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This study aimed to assess the biological activities of Tunisian Simmondsia chinensis and characterize their potential bioactive compounds. Different extracts of S. chinensis were tested for their antioxidant, antibacterial, anti α-amylase, and anti-acetylcholinesterase activities through in vitro assays. The methanolic extract exhibited the highest levels of antioxidant activity and total phenolic content (976.03 GAE/g extract) compared to the other extracts. Additionally, it demonstrated a substantial anti-acetylcholinesterase activity (PI= 75%) and potent antibacterial property, particularly against Enterococcus faecalis, Listeria monocytogenes, Bacillus cereus, Bacillus subtilis, and Salmonella enterica. The IC50 values of ethyl acetate and methanolic extracts against α-amylase were 42 μg/mL and 40 μg/mL, respectively, indicating potent anti-diabetic effects. HPLC-ESI-MS/MS analyses identified flavonoids and lignans as the major phenolic compounds in the methanolic extract. To better comprehend the mechanisms behind inhibitory effects on α-amylase and acetylcholinesterase enzymes, a molecular docking study was conducted. Consequently, these findings indicate that S. chinensis is a highly valuable natural resource with potential industrial applications., (© 2024 Wiley‐VCH GmbH.)

In this study, a novel fatty acid anhydride, named phalarisin 1, was successfully isolated from the ethyl acetate extract of Phalaris canariensis growing in Tunisia. The structural characterisation of the compound was achieved through various spectroscopic techniques including FT-IR, 1D and 2D-NMR spectroscopy, as well as acidic hydrolysis analyses. Remarkably, phalarisin exhibited potent antimicrobial properties against a range of pathogens including Micrococcus luteus , Bacillus subtilis , Fusarium oxysporum , and Fusarium phylophylum , with minimum inhibitory concentrations (MICs) ranging from 31.25 to 62.5 μg/mL. To grasp the antimicrobial potential of compound 1, molecular docking studies were performed and they furnished evidence indicating its ability to bind to proteins in bacteria and fungi that are pivotal for drug resistance.

During the search for protein tyrosine phosphatase 1B (PTP1B) inhibitory compounds from the natural resources, two new serratane triterpenes, 3-O-dihydro-p-coumaroyltohogenol (1) and 21-O-acetyltohogenol (2), along with four known serratane triterpenes (3-6), were isolated from the whole plant of Huperzia serrata. The chemical structures of compounds 1 and 2 were determined by NMR study, HRMS analysis, and chemical modification. All isolates were evaluated for their PTP1B inhibitory activities. Among the isolates, compounds 1, 3, 5 and 6 exhibit moderate inhibitory activities against PTP1B. Kinetic studies demonstrated that they are competitive inhibitors. Molecular docking studies support these experimental results by showing that compounds 1, 3, 5 and 6 interact with the active site of PTP1B, clarifying the structure-activity relationship. This study suggests that serratane triterpenes from H. serrata have potential as starting skeletons for anti-diabetes or anti-obesity agents., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Monocarbonyl analogs of curcumin (MACs) represent structurally modified versions of curcumin. The existing literature indicates that MACs exhibit enhanced anticancer properties compared with curcumin. Numerous research articles in recent years have emphasized the significance of MACs as effective anticancer agents. This review focuses on the latest advances in the anticancer potential of MACs, from 2014 to 2024, including discussions on their mechanism of action, structure-activity relationship (SAR), and in silico molecular docking studies., (© 2024 Deutsche Pharmazeutische Gesellschaft.)

Three carboxamide-based ligands and their iron(III) complexes were prepared and structurally characterized. Analytical, thermal and mass spectra measurements showed a 1:1 stoichiometric (M:L) of the synthesized iron(III) complexes. The distorted octahedral geometry of the present iron(III) complexes was assigned based on the results of spectroscopy and magnetometry. Processing of X-ray diffraction data for powder samples by the software Expo 2014 confirmed the octahedral geometry of the three iron(III) complexes. Electrochemical properties of the present iron(III) complexes were studied by cyclic voltammetric measurements. The present iron(III) complexes exhibit SOD like activity with IC 50 values of 16.45, 15.24 and 9.70 μM. The drive forces (-λ or Δ G °) controlling these biocatalytic reactions were determined and correlated with catalytic activity. The proposed catalytic mechanistic implications for the conversion of O 2 •- to H 2 O 2 and H 2 O were discussed. The antimicrobial activity has been studied in vitro against G(+) and G(-) pathogenic bacteria. The in vitro anticancer activity of the carboxamide-based ligands and their iron(III) complexes against human Hepatocellular carcinoma (HepG-2) cell lines was examined. The obtained results demonstrated the potent anticancer activity of iron(III) complexes with increased safety on normal cells compared to cisplatin. Molecular docking calculations confirmed the experimental findings of the antibacterial and anticancer activities of both free ligands and their iron(III) chelates.Communicated by Ramaswamy H. Sarma.

This study determined chemical profiles, antibacterial and antibiofilm activities of the essential oils (EOs) obtained by A. visnaga aerial parts and F. vulgare fruits. Butanoic acid, 2-methyl-, 3-methylbutyl ester (38.8%), linalyl propionate (34.7%) and limonene (8.5%) resulted as main constituents of A. visnaga EO. In F. vulgare EO trans-anethole (76.9%) and fenchone (14.1%) resulted as main components. The two EOs were active against five bacterial strains (Acinetobacter baumannii, Escherichia coli, Listeria monocytogenes, Pseudomonas aeruginosa, and Staphylococcus aureus) at different degrees. The MIC values ranged from 5 ± 2 to 10 ± 2 μL/mL except for S. aureus (MIC >20 μL/mL). EOs exhibited inhibitory effect on the formation of biofilm up to 53.56 and 48.04% against E. coli and A. baumannii, respectively and activity against bacterial metabolism against A. baumannii and E. coli, with biofilm-inhibition ranging from 61.73 to 73.55%. The binding affinity of the identified components was estimated by docking them into the binding site of S. aureus gyrase (PDB code 2XCT) and S. aureus tyrosyl-tRNA synthetase (PDB code 1JIJ). trans-Anethole and butanoic acid, 2-methyl-, 3-methylbutyl ester showed relatively moderate binding interactions with the amino acid residues of S. aureus tyrosyl-tRNA synthetase. In addition, almost all predicted compounds possess good pharmacokinetic properties with no toxicity, being inactive for cytotoxicity, carcinogenicity, hepatotoxicity, mutagenicity and immunotoxicity parameters. The results encourage the use of these EOs as natural antibacterial agents in food and pharmaceutical industries., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

In the current study, a new series of benzenesulfonamides 6a-r was designed and synthesized as dual VEGFR-2 and FGFR1 kinase inhibitors with anti-cancer activity. The 4-trifluoromethyl benzenesulfonamide 6l exhibited the highest dual VEGFR-2/FGFR1 inhibitory activity with IC 50 values of 0.025 and 0.026 µM, respectively. It showed a higher activity than sorafenib and staurosporine by 1.8- and 1.3-fold, respectively. Furthermore, compound 6l was further tested on EGFR and PDGFR-β kinases showing IC 50 values of 0.106 and 0.077 µM, respectively. The target compounds were tested for their anticancer activity against NCI-60 panel of cancer cell lines at 10 µM concentration, where compound 6l displayed the highest mean growth inhibition percent % (GI%) of 60.38%. Compounds 6a, 6b, 6e, 6f, 6h-l, and 6n-r revealed promising GI% on breast cancer cell lines (MCF-7, T-47D, and MDA-MB-231), and were subjected to IC 50 determination on these cell lines. The tested compounds showed a higher activity on T-47D and MCF-7 cell lines over MDA-MB-231 cell line compared to the used reference standard; sorafenib. Compounds 6e, 6h-j, 6l and 6o revealed IC 50 values ≤ 20 µM against T-47D cell line, furthermore, they were found to be non-cytotoxic on Vero normal cell line. Furthermore, the effect of the most active compounds 6i, and 6l in T-47D cells on cell cycle analysis progression, cell apoptosis, and apoptosis markers was investigated. Both compounds arrested cell cycle progression at G1 phase, furthermore, they enhanced early and late apoptosis, as well as necrosis. The capability of compounds 6i, and 6l to induce apoptosis was further confirmed by their ability to raise BAX/BCl-2 ratio and caspase-3 level in the treated cells. Cell migration assay revealed that both compounds 6i and 6l have anti-migratory effects compared to control T-47D cells after 24, and 48 h. Molecular docking studies for compounds 6a-r on VEGFR-2 and FGFR1 binding sites showed that they exhibit an analogous binding mode in both target kinases which agrees with that of type II kinase inhibitors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In Vietnam, the stems and roots of the Rutaceous plant Paramignya trimera (Oliv.) Burkill (known locally as "Xáo tam phân") are widely used to treat liver diseases such as viral hepatitis and acute and chronic cirrhosis. In an effort to search for Vietnamese natural compounds capable of inhibiting coronavirus based on molecular docking screening, two new dimeric coumarin glycosides, namely cis-paratrimerin B (1) and cis-paratrimerin A (2), and two previously identified coumarins, the trans-isomers paratrimerin B (3) and paratrimerin A (4), were isolated from the roots of P. trimera and tested for their anti-angiotensin-converting enzyme 2 (ACE-2) inhibitory properties in vitro. It was discovered that ACE-2 enzyme was inhibited by cis-paratrimerin B (1), cis-paratrimerin A (2), and trans-paratrimerin B (3), with IC 50 values of 28.9, 68, and 77 µM, respectively. Docking simulations revealed that four biscoumarin glycosides had good binding energies (∆G values ranging from -10.6 to -14.7 kcal/mol) and mostly bound to the S1' subsite of the ACE-2 protein. The key interactions of these natural ligands include metal chelation with zinc ions and multiple H-bonds with Ser128, Glu145, His345, Lys363, Thr371, Glu406, and Tyr803. Our findings demonstrated that biscoumarin glycosides from P. trimera roots occur naturally in both cis- and trans-diastereomeric forms. The biscoumarin glycosides Lys363, Thr371, Glu406, and Tyr803. Our findings demonstrated that biscoumarin glycosides from P. trimera roots hold potential for further studies as natural ACE-2 inhibitors for preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

A series of novel chromone derivatives of (N-(4-oxo-2-(trifluoromethyl)-4H-chromen-6-yl) benzamides) were synthesized by treating 7-amino-2-(trifluoromethyl)-4H-chromen-4-one with K 2 CO 3  and/or NaH, suitable alkyl halides and acetonitrile and/or 1,4-dioxane. The obtained products are in high yields (87 to 96%) with various substituents in short reaction times with no more by-products and confirmed by FT-IR,  1 H, and  13 C-NMR Spectral data. The in vitro cytotoxic activity was examined against two human cancer cell lines, namely the human lung adenocarcinoma (A-549) and the human breast (MCF-7) cancer cell line. Compound 4h showed promising cytotoxicity against both cell lines with IC 50  values of 22.09 and 6.40 ± 0.26 µg/mL respectively, compared to that of the standard drug. We also performed the in vitro antioxidant activity by DPPH radical, hydrogen peroxide, NO scavenging, and total antioxidant capacity (TAC) assay methods, and they showed significant activities. The possible binding interactions of all the synthesized chromone derivatives are also investigated against selective pharmacological targets of human beings, such as HERA protein for cytotoxic activity and Peroxiredoxins (3MNG) for antioxidant activity which showed closer binding free energies than the standard drugs and evidencing the above two types of activities., (© 2024. The Author(s).)

Introduction: D-pinitol, a naturally occurring inositol, has diverse biological activities like antioxidant, antimicrobial and anticancer activities. This study aimed to evaluate anti-inflammatory effect of d-pinitol in a chick model. Additionally, in silico studies were performed to evaluate the molecular interactions with cyclooxygenase-2 (COX-2). Methods: The tested groups received d-pinitol (12.5, 25, and 50 mg/kg) and the standard drugs celecoxib and ketoprofen (42 mg/kg) via oral gavage prior to formalin injection. Then, the number of licks was counted for the first 10 min, and the paw edema diameter was measured at 60, 90, and 120 min. Results and Discussion: The d-pinitol groups significantly ( p < 0.05) reduced the number of paw licks and paw edema diameters, compared to negative control. When d-pinitol was combined with celecoxib, it reduced inflammatory parameters more effectively than the individual groups. The in silico study showed a promising binding capacity of d-pinitol with COX-2. Taken together, d-pinitol exerted anti-inflammatory effects in a dose-dependent manner, possibly through COX-2 interaction pathway., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Haque, El-Nashar, Akbor, Alfaifi, Bappi, Chowdhury, Hossain, El-Shazly, Albayouk, Saleh and Islam.)

Helicobacter pylori causes severe stomach disorders and the use of enzyme inhibitors for treatment is one of the possible therapies. The great biological potential of imine analogs as urease inhibitors has been the focus of researchers in past years. In this regard, we have synthesized twenty-one derivatives of dichlorophenyl hydrazide. These compounds were characterized by different spectroscopic techniques i.e. NMR and HREI-MS. Compounds 2 and 10 were found to be the most active in the series. Structure-activity relationship has been established for all compounds based on different substituents attached to the phenyl ring that play a vital role in enzyme inhibition. From the structure-activity relationship, it has been observed that these analogs showed excellent potential for urease and can be an alternate therapy in the future. The molecular docking study was performed to further explore the binding interactions of synthesized analogs with enzyme active sites.Communicated by Ramaswamy H. Sarma.

A new series of 6-(4-fluorophenyl)-2-(methylthio) pyrimidine-5-carbonitrile derivatives were designed and synthesized as EGFR/PI3K dual inhibitors, and potential antiproliferative agents. The new 22 compounds were screened by DTP-NCI against all NCI60 cell lines. Almost all compounds showed cytotoxic activity. Compound 7c showed a promising antitumour activity on CNS cancer (SNB-75), and ovarian cancer (OVAR-4) with IC 50  < 0.01, and 0.64 µM, respectively. Fortunately, 7c exhibited a better safety profile on normal cells (WI-38) than doxorubicin by 2.2-fold. Compound 7c displayed selective inhibitory activity on EGFR t790m over EGFR WT with IC 50  = 0.08, and 0.13 µM, respectively, wherefore it might overcome EGFR-TKIs resistance. In addition to its remarkable inhibitory activity on all PI3K isoforms, specifically PI3K-δ with IC 50  = 0.64 µM Compared with LY294002 IC 50  = 7.6 µM. Compound 7c arrested the cell cycle of SNB-75 & OVAR-4 at the G0-G1 phase coupled with apoptosis induction. The western blotting analysis approved decreasing the expression level of p-AKT coupled with an increase in Casp3, Casp9, and BAX proteins in the SNB-75 & OVAR-4 after being treated with 7c which may support the suggested mechanism of action of 7c as EGFR/PI3K dual inhibitor. Physicochemical parameters were forecasted using SwissADME online tool. MD showed the interaction of 7c with the crucial amino acids of the active domain of both EGFR/PI3K which may explain its potent inhibitory activities. In vivo study disclosed a significant decrease in tumor weight and the number of nodules in the group of mice treated with 7c compared with the control group., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

A series of 2'-hydroxychalcone derivatives with various substituents on B-ring were synthesized and evaluated for AMP-activated protein kinase (AMPK) activation activity in podocyte cells. The results displayed that hydroxy, methoxy and methylenedioxy groups on B-ring could enhance the activitiy better than O-saturated alkyl, O-unsaturated alkyl or other alkoxy groups. Compounds 27 and 29 possess the highest fold change of 2.48 and 2.73, respectively, which were higher than those of reference compound (8) (1.28) and metformin (1.88). Compounds 27 and 29 were then subjected to a concentration-response study to obtain the EC 50 values of 2.0 and 4.8 µM, respectively and MTT assays also showed that cell viability was not influenced by the exposure of podocytes to compounds 27 and 29 at concentrations up to 50 μM. In addition, compound 27 was proved to activate AMPK via calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-dependent pathway without affecting intracellular calcium levels. The computational study showed that the potent compounds exhibited stronger ligand-binding strength to CaMKKβ, particularly compounds 27 (-8.4 kcal/mol) and 29 (-8.0 kcal/mol), compared to compound 8 (-7.5 kcal/mol). Fragment molecular orbital (FMO) calculation demonstrated that compound 27 was superior to compound 29 due to the presence of methyl group, which amplified the binding by hydrophobic interactions. Therefore, compound 27 would represent a promising AMPK activator for further investigation of the treatment of diabetes and diabetic nephropathy., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Warinthorn Chavasiri reports financial support was provided by Chulalongkorn University. Warinthorn Chavasiri reports a relationship with Chulalongkorn University that includes: employment., (Copyright © 2023 Elsevier Inc. All rights reserved.)

We report in this work a synthesis of novel triazolo[1,5]benzodiazepine derivatives by the 1,3-dipolar cycloaddition reaction of N-aryl-C-ethoxycarbonylnitrilimines with 1,5-benzodiazepines. All the structures of the new compounds were determined from their NMR ( 1 H and 13 C) and HRMS. Then, X-ray crystallography analysis of compound 4d confirmed the stereochemistry of cycloadducts. The compounds 1 , 4a-d , 5a-d , 6c , 7 and 8 were evaluated for their in vitro anti-diabetic activity against α-glucosidase. The compounds 1, 4d, 5a and 5b showed potential inhibitory activities compared to standard acarbose. Additionally, an in silico docking study was conducted to look into the active binding mode of the synthesized compounds within the target enzyme.Communicated by Ramaswamy H. Sarma.

Several generations of anti-epileptic drugs (AEDs) are available but have several associated side effects apart from a limited success rate. Drug repositioning strategies have gained importance in the last two decades owing to lower failure rates and economic burden. Drugs with similar side effect profiles may share a common mechanism of action and thus can be linked to other disease treatments. The present study was carried out to identify the newly approved drug candidate(s) as AEDs using clinical side-effects drug repositioning strategy. The clinical side effect similarity of drugs available in the SIDER v4.1 database was estimated against common side effects of 5 major marketed AEDs, using the 'dplyr' package library in the R. Further drugs were filtered based on Blood Brain Barrier permeability prediction and FDA-approval status. Molecular docking studies were performed for selected 26 hits (drugs) against previously identified epilepsy target receptors: Voltage-gated sodium channel α2 (Nav1.2), GABA receptor α1-β1 (GABAr α1-β1), and Voltage-gated calcium channel α-1 G (Cav3.1). Only 2 drugs (Ziprasidone and Paroxetine) showed better binding affinities against studied epilepsy receptors Nav1.2, GABAr α1-β1, and Cav3.1, than their corresponding standard AEDs, i.e. Carbamazepine, Clonazepam, and Pregabalin, respectively. Ziprasidone reportedly showed seizure-like symptoms in ∼3% of patients and was hence omitted from further study. The MDS study of docked complexes of Paroxetine with selected epilepsy target receptors showed stable RMSD values and better interaction energies. The study reveals Paroxetine as a potential candidate to be repurposed for 1st line epileptic seizure medication.Communicated by Ramaswamy H. Sarma.

Introduction: Drug resistance to existing antimicrobial drugs has become a serious threat to human health, which highlights the need to develop new antimicrobial agents., Methods: In this study, a new set of 3-hydroxypyridine-4-one derivatives (6a-j) was synthesized, and the antimicrobial effects of these derivatives were evaluated against a variety of microorganisms using the microdilution method. The antimicrobial evaluation indicated that compound 6c, with an electron-donating group -OCH 3 at the meta position of the phenyl ring, was the most active compound against S. aureus and E. coli species with an MIC value of 32 μg/mL. Compound 6c was more potent than ampicillin as a reference drug., Results: The in vitro antifungal results showed that the studied derivatives had moderate effects (MIC = 128-512 μg/mL) against C. albicans and A. niger species. The molecular modeling studies revealed the possible mechanism and suitable interactions of these derivatives with the target protein., Conclusion: The obtained biological results offer valuable insights into the design of more effective antimicrobial agents., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

A library of 1, 2, 3-triazole incorporated thiazolylcarboxylate derivatives (7a-q) and (8a-j) were synthesized and evaluated for their in-vitro antitubercular activity against Mycobacterium tuberculosis H37Rv. The two compounds 7h and 8h have displayed excellent antitubercular activity with MIC values of 3.12 and 1.56 µg/mL respectively (MIC values of standard drugs; Ciprofloxacin 1.56 μg/mL & Ethambutol 3.12 μg/mL). Whereas, the four compounds 7i, 7n, 7p and 8i displayed noticeable antitubercular activity with a MIC value of 6.25 µg/mL. The active compounds of the series were further studied for their cytotoxicity against RAW264.7 cell line using MTT assay. Furthermore, to study the probable mechanism of antitubercular action, physicochemical property profiling, DFT calculation and molecular docking study were executed on mycobacterial cell wall target Decaprenylphosphoryl-β-d-ribose 2'-epimerase 1 (DprE1). Among all the compounds, 7h (-10 kcal/mol) and 8h (-10.1 kcal/mol) exerted the highest negative binding affinity against the targeted DprE1 (PDB: 4NCR) protein., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: In this study, a simple triethylammonium salt of phosphoric acid (triethylammonium dihydrogen phosphate) (4) in the liquid state was utilized as an inexpensive, efficient one-pot three components, solvent-free synthesis of thiazolidine-4-one derivatives, with good to excellent yields. Techniques such as FT-IR, 1 H-NMR, 13 C-NMR, 13 C-NMR-DEPT-135, and MS. were used for the structural elucidation. The high biotic efficiency of the newly obtained compounds was confirmed by in vitro antimicrobial action against Gram-positive ( S. Aureus ), Gram-negative bacteria ( P. Aeruginosa and E. Coli ) and antifungal activity ( C. Albicans ) via microplate titer dilution technique. Finally, a molecular docking study was performed with a resolved crystal structure of S. Aureus D-alanine alanyl carrier protein ligase (PDB ID: 7VHV). This investigation aimed to synthesize a new series of thiazolidine-4-one derivatives combined with benzoxazole moiety., Material and Methods: Ionic liquid assistance one-pot solvent-free synthesis method used to synthesize a new series of thiazolidine-4-one derivative 10(a-e)., Results: Structural identification of new synthesis and biological evaluation via techniques of (IR, 1 H-NMR, 13 C-NMR, 13 C-NMR-DEPT-135, and MS)., Conclusion: Ionic liquid is utilized as an inexpensive, efficient one-pot three-component solvent-free synthesis of thiazolidine-4-one derivatives with good to excellent yields. Most of the synthesized compounds showed high biological and anti-fungal activity, in line with the docking study against mentioned microorganism and crystal structure of PDB (ID: 7VHV), respectively., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: 4-Methylacetophenone is used in the preparation of starting materials, 4-methylphenacyle bromide ( 2 ) and 4-methylacetophenone thiosemicarbazole ( 3 ). Results: Several novel 2,4-disubstituted-1,3-thiazole analogues were obtained via the treatment of starting materials with 4-methylphenacyl bromide, acetyl chloride, aromatic aldehydes and bromination providing thiazole derivatives 5-8 respectively. Conclusion: Compounds 5-8 were investigated for their cytotoxic activity on MCF-7 and normal breast cells. Active compounds were found and in contrast to staurosporine, compound 8 displayed the most potent cytotoxic action that showed a strong inhibitory effect (aromatase) and (protein tyrosine kinase) enzymes, proving that the novel thiazole derivatives promoted the effective anticancer drug candidates.

Network pharmacology is an emerging pioneering approach in the drug discovery process, which is used to predict the therapeutic mechanism of compounds using various bioinformatic tools and databases. Emerging studies have indicated the use of network pharmacological approaches in various research fields, particularly in the identification of possible mechanisms of herbal compounds/ayurvedic formulations in the management of various diseases. These techniques could also play an important role in the prediction of the possible mechanisms of neuroprotective compounds. The first part of the chapter includes an introduction on neuroprotective compounds based on literature. Further, network pharmacological approaches are briefly discussed. The use of network pharmacology in the prediction of the neuroprotective mechanism of compounds is discussed in detail with suitable examples. Finally, the chapter concludes with the current challenges and future prospectives., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Alzheimer's disease (AD) is a degenerative neurological condition that severely affects the elderly and is clinically recognised by a decrease in cognition and memory. The treatment of this disease has drawn considerable attention and sparked increased interest among the researchers in this field as a result of a number of factors, including an increase in the population of patients over time, a significant decline in patient quality of life, and the high cost of treatment and care. The current work was carried out for the synthesis of benzimidazole-oxazole hybrid derivatives as efficient Alzheimer's inhibitors and as a springboard for investigating novel anti-chemical Alzheimer's prototypes. The inhibition profiles of each synthesised analogue against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes were assessed. All the synthesized benzimidazole-based oxazole analogues displayed a diverse spectrum of inhibitory potentials against targeted AChE and BuChE enzymes when compared to the reference drug donepezil (IC 50 = 2.16 ± 0.12 M and 4.50 ± 0.11 µM, respectively). The most active AChE and BuChE analogues were discovered to be analogues 9 and 14, with IC 50 values of 0.10 ± 0.050 and 0.20 ± 0.050 µM (against AChE) and 0.20 ± 0.050 and 0.30 ± 0.050 µM (against BuChE), respectively. The nature, number, position, and electron-donating and -withdrawing effects on the phenyl ring were taken into consideration when analysing the structure-activity relationship (SAR). Molecular docking studies were also carried out on the active analogues to find out how amino acids bind to the active sites of the AChE and BuChE enzymes that were being studied., Competing Interests: The authors declare no conflict of interest.

The development and discovery of steroidal drugs to cure cervical cancer is of the most important. The Claisen condensation of androstene and estrone with aromatic aldehydes was catalyzed by potassium tert. butoxide in tert. butanol to give the corresponding 2-arylidene and 16-arylidene estrone. Subsequently, the 16-arylidene estrone reacted with acid chloride in presence of quaternary amine in halogenated solvent resulting in the steroidal arylidene derivatives. Synthesis, Characterization and in vitro cytotoxic activity of arylidenes are rationalized. Fifteen compounds are synthesized and six of them were evaluated for cytotoxic activity against cervical cancer cell line. HT-3 cell line examination revealed a considerable growth inhibition. Compounds 4a, 4b, 6b, 8c, and 8d, which are estrone-based arylidenes, are the most potent of the series, with IC 50 value of 7.15, 10.76, 6.37, 3.56, and 1.55 µM/ml against HT-3 cell line. In addition, molecular docking studies were performed for the steroidal arylidenes to elucidate the binding interactions. Compound 4a, 4b, 6b, 8c and 8d showed excellent binding energy. Docking studies agreed well with in vitro studies. The end result offers an alternative approach to develop steroidal arylidenes that are more effective and are based on estrone, leading to the development of novel anticancer agents., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

4-((4-(1-benzyl-2-methyl-4-nitro-1 H -imidazole-5-yl)piperazine-1-yl)methyl)-1-substituted-1 H -1,2,3-triazole motifs are designed and synthesized via click chemistry. The reaction of 1-( N 1 -benzyl- 2-methyl-4-nitro-1 H -imidazole- 5-yl)-4-(prop-2-yn-1-yl) piperazine 5 as new scaffold with diverse primary azides to selectively produce 1,4-disubstituted-1,2,3-triazoles 9a - k, 10a - c and 11a - q . Physicochemical methods: when 1 H NMR, 13 C NMR, and HRMS are utilized to fully characterize all synthesized compounds. X-ray structural determination and analysis for compound 9a is also performed. The newly designed chromophores are assessed for their anti-proliferative potency against three selected human cancer cell lines (MCF-7, HepG2, and PC3), and one normal cell line (Dermal/Fibroblast). Compounds 9g and 9k have shown potent activities against the MCF-7 cell line with IC 50 values of (2.00 ± 0.03 μM) and (5.00 ± 0.01 μM) respectively. ADMET studies and Molecular docking investigations are performed on the most active hybrid nitroimidazole derivatives 9g and 9k with 4-hydroxytamoxifen ( 4-OHT ) at the human estrogen receptor alpha (hER) during binding active sites to study the ligand-protein interactions and free binding energies at atomic levels. The triazole ring in the 9g derivative forms a hydrogen bond with Asp58 with distance 3.2 Å. And it is found that polar contact with His231 amino acid residue. In silico assessment of the compounds showed very good pharmacokinetic properties based on their physicochemical values, also the ADMET criteria of the most active hybrid systems are within the acceptable range., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Based on the use of quercetin for treating diabetes and H 2 S for promoting wound healing, a series of three quercetin-linker-H 2 S donor conjugates was designed, synthesized and characterized by 1 H-NMR, 13 C-NMR and MS. Meanwhile, in vitro evaluation of these compounds was also researched by IR-HepG2 treatment experiment, MTT assay, scratch test and tubule formation experiment. The three compounds could be used to treat insulin resistance induced by high glucose and promote the proliferation of human umbilical vein endothelial cells, wound healing, and the formation of tubules in vitro under a high-glucose environment. Our results illustrate that these compounds could be used to treat diabetes and promote wound healing at the same time. Furthermore, molecular docking study results of the compounds were consistent with the evaluated biological activity. In vivo research of compounds is underway., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Despite the widespread and easy access to NSAIDs, effective and safe treatment of various inflammatory disorders is still a serious challenge because of the severe adverse effects distinctive to these drugs. The Mannich base derivatives of pyrrolo[3,4- c ]pyrrole are potent, preferential COX-2 inhibitors with a COX-2/COX-1 inhibitory ratio better than meloxicam. Therefore, we chose the six most promising molecules and subjected them to further in-depth research. The current study presents the extensive biological, spectroscopic and in silico evaluation of the activity and physicochemical properties of pyrrolo[3,4- c ]pyrrole derivatives. Aware of the advantages of dual COX-LOX inhibition, we investigated the 15-LOX inhibitory activity of these molecules. We also examined their antioxidant effect in several in vitro experiments in a protection and regeneration model. Furthermore, we defined how studied compounds interact with artificial models of cell membranes, which is extremely important for drugs administered orally with an intracellular target. The interactions and binding mode of the derivatives with the most abundant plasma proteins-human serum albumin and alpha-1-acid glycoprotein-are also described. Finally, we used computational techniques to evaluate their pharmacokinetic properties. According to the obtained results, we can state that pyrrolo[3,4- c ]pyrrole derivatives are promising anti-inflammatory and antioxidant agents with potentially good membrane permeability.

Caffeic acid phenethyl ester (CAPE), a main active component of propolis and a flavonoid, is one of the natural products that has attracted attention in recent years. CAPE, which has many properties such as anti-cancer, anti-inflammatory, antioxidant, antibacterial and anti-fungal, has shown many pharmacological potentials, including protective effects on multiple organs. Interestingly, molecular docking studies showed the possibility of binding of CAPE with replication enzyme. In addition, it was seen that in order to increase the binding security of the replication enzyme and CAPE, modifications can be made at three sites on the CAPE molecule, which leads to the possibility of the compound working more powerfully and usefully to prevent the proliferation of cancer cells and reduce its rate. Also, it was found that CAPE has an inhibitory effect against the main protease enzyme and may be effective in the treatment of SARS-CoV-2. This review covers in detail the importance of CAPE in alternative medicine, its pharmacological value, its potential as a cancer anti-proliferative agent, its dual role in radioprotection and radiosensitization, and its use against coronavirus disease 2019 (COVID-19)., (© 2022 John Wiley & Sons Ltd.)

The treatment of advanced non-small cell lung cancer (NSCLC) has made substantial progress due to the rapid development of small molecule targeted therapy, with dramatically prolonged survival. As an effective drug for the treatment of NSCLC, epidermal growth factor receptor (EGFR) inhibitors are currently experiencing issues like severe adverse events and drug resistance. It is urgent to develop novel types of EGFR inhibitors to overcome the abovementioned limitations. Pyrrole always works well as a probe for the creation of novel medication candidates for hard-to-treat conditions like lung cancer. Although the design, synthesis, and biological assays of pyrrole derivatives have been reported, their inhibitory actions against the receptor tyrosine kinase (RTK) EGFR have not been in-depthly studied. This review highlights the small molecule EGFR inhibitors containing pyrrole heterocyclic pharmacophores in recent years, and the research on their mechanism, biological activity, and structure-activity relationship (SAR)., (© 2022 John Wiley & Sons Ltd.)

Background: The compounds containing heterocyclic cores with O, N and/or S atoms are bioactive and valuable molecules in the field of drug discovery and development. There are several applications in different areas for the molecules having oxadiazole moiety in their structures viz. herbicides and corrosion inhibitors, electron-transport materials, polymers and luminescent materials. Hence, demand for new anticonvulsant, antibacterial and analgesic agents has turned into an imperative assignment in the area of medicinal chemistry to improve therapeutic efficacy as well as safety., Methods: In the journey of new anticonvulsive, antibacterial and analgesic molecules with better potency, some newer Oxadiazole analogues were attained by a sequence of synthetic steps with the substituted acrylic acids. IR and 1 H-NMR spectral data were used for the structure elucidation of obtained chemical compounds. In this perspective, the anticonvulsant, antibacterial and analgesic activities were evaluated for synthetically obtained newer chemical moieties. Furthermore, a molecular docking study was performed to elucidate the binding modes of synthesized ligands in the active pockets of Cox-1/2 enzymes, DNA Gyrase and GABA inhibitors., Results: It has been observed that all the synthetic molecules showed good analgesic activity while A1 molecule demonstrated better analgesic activity. In the case of anticonvulsant and antibacterial activity among other ligands, C1 molecule possessed profound anticonvulsant activity whereas B1 molecule showed maximum antibacterial activity and molecular docking study also endorsed the same consequences., Conclusion: It might be recognized from the present study that prepared compounds are distinctive in lieu of their structure and noticeable biological activity. In the quest for a newer group of anticonvulsant, antibacterial and analgesic molecules, these compounds might be useful for the society., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Triazole-based thiosemicarbazone derivatives ( 6a-u ) were synthesized then characterized by spectroscopic techniques, such as 1HNMR and 13CNMR and HRMS (ESI). Newly synthesized derivatives were screened in vitro for inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes. All derivatives (except 6c and 6d , which were found to be completely inactive) demonstrated moderate to good inhibitory effects ranging from 0.10 ± 0.050 to 12.20 ± 0.30 µM (for AChE) and 0.20 ± 0.10 to 14.10 ± 0.40 µM (for BuChE). The analogue 6i (IC 50 = 0.10 ± 0.050 for AChE and IC 50 = 0.20 ± 0.050 µM for BuChE), which had di-substitutions (2-nitro, 3-hydroxy groups) at ring B and tri-substitutions (2-nitro, 4,5-dichloro groups) at ring C, and analogue 6b (IC 50 = 0.20 ± 0.10 µM for AChE and IC 50 = 0.30 ± 0.10 µM for BuChE), which had di-Cl at 4,5, -NO 2 groups at 2-position of phenyl ring B and hydroxy group at ortho-position of phenyl ring C, emerged as the most potent inhibitors of both targeted enzymes (AChE and BuChE) among the current series. A structure-activity relationship (SAR) was developed based on nature, position, number, electron donating/withdrawing effects of substitution/s on phenyl rings. Molecular docking studies were used to describe binding interactions of the most active inhibitors with active sites of AChE and BuChE.

Xanthine derivatives have been a great area of interest for the development of potent bioactive agents. Thirty-eight methylxanthine derivatives as acetylcholinesterase inhibitors (AChE) were designed and synthesized. Suzuki-Miyaura cross-coupling reactions of 8-chlorocaffeine with aryl(hetaryl)boronic acids, the CuAAC reaction of 8-ethynylcaffeine with several azides, and the copper(I) catalyzed one-pot three-component reaction (A 3 -coupling) of 8-ethynylcaffeine, 1-(prop-2-ynyl)-, or 7-(prop-2-ynyl)-dimethylxanthines with formaldehyde and secondary amines were the main approaches for the synthesis of substituted methylxanthine derivatives (yield 53-96%). The bioactivity of all new compounds was evaluated by Ellman's method, and the results showed that most of the synthesized compounds displayed good and moderate acetylcholinesterase (AChE) inhibitory activities in vitro. The structure-activity relationships were also discussed. The data revealed that compounds 53 , 59 , 65 , 66 , and 69 exhibited the most potent inhibitory activity against AChE with IC 50 of 0.25, 0.552, 0.089, 0.746, and 0.121 μM, respectively. The binding conformation and simultaneous interaction modes were further clarified by molecular docking studies.

The slow solvent evaporation approach was used to create a single crystal of (C 7 H 6 N 3 O 2 ) 2 [ZnCl 4 ] at room temperature. Our compound has been investigated by single-crystal XRD which declares that the complex crystallizes in the monoclinic crystallographic system with the P 2 1 / c as a space group. The molecular arrangement of the compound can be described by slightly distorted tetrahedral ZnCl 4 2- anionic entities and 5-nitrobenzimidazolium as cations, linked together by different non-covalent interaction types (H-bonds, Cl…Cl, π…π and C-H…π). Hirshfeld's surface study allows us to identify that the dominant contacts in the crystal building are H…Cl/Cl…H contacts (37.3%). FT-IR method was used to identify the different groups in (C 7 H 6 N 3 O 2 ) 2 [ZnCl 4 ]. Furthermore, impedance spectroscopy analysis in 393 ≤ T ≤ 438 K shows that the temperature dependence of DC conductivity follows Arrhenius' law. The frequency-temperature dependence of AC conductivity for the studied sample shows one region (E a = 2.75 eV). In order to determine modes of interactions of compound with double stranded DNA, molecular docking simulations were performed at molecular level.

A novel series of 2-(2- oxoethyl)pyrimidine-5-carboxamide derivatives were designed, synthesized and evaluated as acetylcholinesterase inhibitors (AChEIs) for the treatment of Alzheimer's disease (AD). Biological activity results demonstrated that compound 10q showed the best inhibitory activity against AChE (IC 50  = 0.88 ± 0.78 μM), which was better than that of Huperzine-A, and its inhibitory effect on BuChE was weak (IC 50  = 10.0 ± 1.30 μM), which indicated that compound 10q was a dominant AChE inhibitor. In addition, the result of molecular docking study displayed that 10q could simultaneously bind to CAS and PAS sites of AChE, which was consistent with the mixed inhibition mode shown by the enzymatic kinetics study of 10q. Furthermore, the molecular properties of the target compounds were predicted online using the molinspiration server and pkCSM, The results exhibited that compound 10q had drug-like properties that satisfied the Lipinski's rule of five. Based on the bioactivity and molecular properties, compound 10q for further development was valuable., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Three new compounds of amidophosphoric acid esters with a [OCH 2 C(CH 3 ) 2 CH 2 O]P(O)[ X ] segment (where X =cyclopentylamido ( 1 ), 2-aminopyridinyl ( 2 ) and pyrrolidinyl ( 3 )) were synthesized and studied using FT-IR and 31 P/ 13 C/ 1 H NMR spectroscopies and single-crystal X-ray diffraction analysis. The compounds crystallize in the triclinic space groups P 1 ‾ for 1 and 3 and in the orthorhombic space group Pca 2 1 for 2 , where the asymmetric unit consists of three symmetrically-independent molecules for 1 and one molecule for 2 and 3 . The intermolecular interactions and supramolecular assemblies are assessed by Hirshfeld surface analysis and enrichment ratios. The results reveal that the substituent effect plays an important role in directing the supramolecular structures. The presence of the aromatic substituent aminopyridine in 2 providing the C-H…π interactions leads to a larger variety in interactions including H…H, H…O/O…H, H…C/C…H and H…N/N…H contacts, whereas the packings of the compounds 1 and 3 bearing aliphatic substituents only include H…H and H…O/O…H contacts. The enrichment ratios affirm the importance of O…H/H…O contacts reflecting the hydrogen bond N-H…O interactions to be the enriched contacts. Compounds 1-3 were also investigated along with five similar reported structures with a [OCH 2 C(CH 3 ) 2 CH 2 O]P(O) segment for their inhibitory behavior against SARS-CoV-2. The molecular docking results illustrate that the presence of the aromatic amido substituent versus the aliphatic type provides a more favorable condition for their biological activities., Competing Interests: The authors declare no conflict of interest., (© 2022 Wiley‐VCH GmbH.)

Ganoderic acid Me (GA-Me) is a natural bioactive compound derived from Ganoderma lucidum . Our present results suggested that GA-Me inhibited proliferation, induced DNA fragmentation and significantly activated caspase-9 and caspase-3 in HCT116 cells. As shown in our previous studies, GA-Me targets several genes to prevent cancer, including colorectal cancer (CRC). Thus, we hypothesized that GA-Me might be a multitarget ligand against cancer. However, its exact mechanism in CRC remains unclear. Here, whole-transcriptome sequencing was employed to assess the long noncoding RNA (lncRNA), circular RNA (circRNA), microRNA (miRNA), and messenger RNA (mRNA) profiles of GA-Me-treated HCT116 cells. In total, 1572 differentially expressed (DE) lncRNAs, 123 DEcircRNAs, 87 DEmiRNAs, and 1508 DEmRNAs were identified. DCBLD2 and RAPGEF5 were validated as two core mRNAs in the DElncRNA, DEcircRNA, and DEmiRNA networks. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed the biological functions and potential mechanisms of TCONS-00008997, XR-925056.2, circRNA-07908, hsa-miR-100-3p, hsa-miR-1257, hsa-miR-3182, NAV3, ADAM20, and STARD4, which were altered after GA-Me treatment. The regulatory relationships of the XR-925056.2-hsa-miR-3182-NAV3/ADAM20/STARD4, circRNA-07908|Chr22:38986298-39025349-hsa-miR-3182-NAV3/ADAM20, ENST00000414039/ENST00000419190-novel874&#95;mature-MMP9 and circRNA-00314|Chr1:35470863-35479212/circRNA-05460|Chr17:72592203-72649268-novel874&#95;mature-MMP9 immune-regulatory networks involved both noncoding RNAs (ncRNAs) and mRNAs. Molecular docking studies showed that Zn 2+ and the His201, His205, His211, Glu202, and Ala165 residues of MMP2 contributed to its high affinity for GA-Me. Zn 2+ and the Glu402 and Gly186 residues of MMP9 are important for its interaction with GA-Me. Our results suggested and confirmed that GA-Me is a potential multitarget lead compound for CRC treatment with unique polypharmacological advantages., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Wan and Zeng.)

Buruli ulcer disease is a neglected necrotizing and disabling cutaneous tropical illness caused by Mycobacterium ulcerans. Fluoroquinolone (FQ), used in the treatment of this disease, has been known to act by inhibiting the enzymatic activities of DNA gyrase. However, the detailed molecular basis of these characteristics and the FQ resistance mechanisms in M. ulcerans remains unknown. This study investigated the detailed molecular mechanism of M. ulcerans DNA gyrase and the contribution of FQ resistance in vitro using recombinant proteins from the M. ulcerans subsp. shinshuense and Agy99 strains with reduced sensitivity to FQs. The IC 50 of FQs against Ala91Val and Asp95Gly mutants of M. ulcerans shinshuense and Agy99 GyrA subunits were 3.7- to 42.0-fold higher than those against wild-type (WT) enzyme. Similarly, the quinolone concentrations required to induce 25% of the maximum DNA cleavage (CC 25 ) was 10- to 210-fold higher than those for the WT enzyme. Furthermore, the interaction between the amino acid residues of the WT/mutant M. ulcerans DNA gyrase and FQ side chains were assessed by molecular docking studies. This was the first elaborative study demonstrating the contribution of mutations in M. ulcerans DNA GyrA subunit to FQ resistance in vitro .

Drug efficiency can be considerably boosted while adverse effects can be reduced by precisely monitoring the concentration of anti-cancer drugs. Thus, one of the most important parameters for human health is the monitoring and detection of anticancer drugs during chemotherapy treatment. Herein, a glassy carbon electrode (GCE) was modified by Pt- and Pd-incorporated ZnO nanoparticles-decorated single-wall carbon nanotubes (Pt-Pd-ZnO/SWCNTs) nanocomposites, and ds-DNA (Calf Thymus) that was a biological recognition element, and it was aimed to be utilized as an ultrasensitive and effective electroanalytical biosensor for idarubicin (IDR) monitoring. Various physicochemical characterization techniques including transmission electron microscopy (TEM), field-emission scanning electron microscopy (FE-SEM) with energy-dispersive X-ray spectroscopy (EDS) were used to investigate the morphology and structure of the Pt-Pd-ZnO/SWCNTs nanocomposite, which was produced via straightforward chemical precipitation combined with the one-pot method. The layer-by-layer modification technique was implemented to fabricate the ds-DNA/Pt-Pd-ZnO/SWCNTs/GCE to be further utilized as a voltammetric sensor for sensitive monitoring of idarubicin in biological fluids and pharmaceutical substances. The electroanalytical method implemented to detect idarubicin was based to detect the ds-DNA's guanine base signal on the surface of the modified electrode in the absence and presence of the anticancer drug. The results explicated that the developed biosensor performed well in determining idarubicin in concentrations ranging from 1.0 nM to 65 μM, with a detection limit of 0.8 nM. The idarubicin detection ability of the modified electrode in real samples was evaluated, and the recovery data was acquired in the range of 98.0% and 104.75%. In the final step, the preferential intercalative binding mode of idarubicin drug with ds-DNA was approved by molecular docking study. This study paves the way for engineering highly sensitive DNA biosensors to be employed in the monitoring of anticancer drugs by combining the benefits of nanocomposites and valuable information of a molecular docking study., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Erlotinib and gefitinib are quinazoline derivatives with antineoplastic properties. Usually, intake of antineoplastic agents results in much a greater degree of oxidative stress, i.e. the production of free radicals, than induced by cancer itself. Hence, anticancerous drugs must also exhibit antioxidant activity but this has not been studied thus far. In this study, the antioxidant activity of erlotinib and gefitinib was examined by experimental and computational studies. It was found that erlotinib and gefitinib exhibit good 2,2-dipheny l-1-picrylhydrazyl (DPPH) radical and hydroxyl radical scavenging (HRS) activities. In DPPH assay, the IC 50 for erlotinib and gefitinib were 0.584 and 0.696 mM, respectively, while IC 50 for HRS assay were 0.843 and 1.03 mM for erlotinib and gefitinib, respectively. Structural characteristics such as frontier molecular orbitals (FMOs), molecular electrostatic potential maps (MESPs), and global descriptive parameters were calculated at DFT/B3LYP/6-311++G (d,p) on the optimized geometries of erlotinib and gefitinib. UV-visible spectroscopy revealed the possible electronic transitions between the FMOs and their associated excitation energies of both drugs and found that erlotinib has π to π* transitions while gefitinib has π to π* and σ to π* transitions. To elucidate the antioxidant activity of erlotinib and gefitinib, three mechanisms namely hydrogen atom transfer (HAT), single electron transfer proton transfer (SETPT), and sequential proton-loss electron-transfer (SPLET) were employed and articulated the results in arithmetic parameters like bond dissociation energy (BDE), proton affinity (PA), ionization potential (IP), electron transfer enthalpy (ETE), and proton dissociation enthalpy (PDE). Further, molecular docking studies have been carried out to have a better understanding of binding sites and modes of interaction with a well-known antioxidant target protein monoamine oxidase-B (MAO-B) employing docking scores and types of interactions. All the calculated parameters point out that though gefitinib and erlotinib were interchangeable, erlotinib requires a lesser amount of energy for proton transfer and electron transfer, moreover it scavenges radicals easily.

Background: In order to make progress in discovering the new agents for cancer treatment with improved properties and considering the fact that 3-hydroxy-3-pyrrolin-2-ones belong to a class of biologically active compounds, we tested series of eleven novels 1,5-diaryl-4-(2- thienylcarbonyl)-3-hydroxy-3-pyrrolin-2-ones for their antitumor potential., Methods: All novel compounds were characterized by spectral (IR, NMR, MS) and elemental analysis. All novel 3-hydroxy-3-pyrrolin-2-ones were screened for their cytotoxic activity on two cancer cell lines, SW480 and MDA-MB 231, and non-transformed fibroblasts (MRC-5)., Results: Compounds B8, B9, and B10 showed high cytotoxicity on SW480 cells together with good selectivity towards MRC-5 cells. It is important to empathize that the degree of selectivity of B8 and B10 was high (SI = 5.54 and 12.09, respectively). Besides, we explored the mechanisms of cytotoxicity of novel derivatives, B8, B9, and B10. The assay showed that tested derivatives induce an apoptotic type of cell death in SW480 cells, with a minor percent of necrotic cells. Additionally, to better understand the suitability of the compounds for potential use as anticancer medicaments, we studied their interactions with biomacromolecules (DNA or BSA). The results indicated that the tested compounds have a great affinity to displace EB from the EB-DNA complex through intercalation. Also, DNA and BSA molecular docking study was performed to predict the binding mode and the interaction region of the compounds., Conclusion: Achieved results indicate that our compounds have the potential to become candidates for use as medicaments., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Chalcone derivative, ethyl 2-(4-(3-(benzo[ b ]thiophen-2yl)acryloyl)phenoxy)acetate ( I ), was synthesized. Compound I was characterized by proton and carbon-13 nuclear magnetic resonance ( 1 H- and 13 C- NMR), fourier transform infrared (FTIR) and mass (LC-ESI-MS/MS) spectroscopic methods. Density Functional Theory (DFT) calculations for compound I were performed at B3LYP/6-311++G(d,p) level. Optimized geometry, frontier molecular orbitals (HOMO; highest occupied molecular orbital; LUMO: lowest unoccupied molecular orbital), IR and NMR parameters of compound I were obtained. The evaluations reveal that the calculation results support the experimental results. The inhibition effects of compound I on cholinesterases and GST enzyme were investigated. K i and inhibition concentration (IC 50 ) values were calculated separately. Ki values of compound I were found for GST 14.19 ± 2.15, for AChE 11.13 ± 1.22 and for BChE 8.74 ± 0.76 recpectively. The docking analysis of compound I supported the enzym inhibition activity exhibiting high inhibition constant and binding energy for three receptors. Compound I is strongly bound to AChE, huBChE and Glutathione S-transferase with binding energies -11.24, -8.56 and -10.39 kcal/mol, respectively.Communicated by Ramaswamy H. Sarma.

JAK inhibitors have been considered as useful targets for the treatment of related diseases. However, first-generation JAK inhibitors have side effects such as anemia, thrombocytopenia, neutropenia and headaches which have been suggested to result from high JAK2 inhibition. Second-generation JAK inhibitors with more specific JAK isozyme inhibition have been studied to eliminate these adverse effects. In this study, novel 4-(1,5- or 2,5-triazole)-pyrrolopyrimidine derivatives with aromatic moieties were synthesized as JAK1 inhibitors, and an in vitro enzyme assay was used to evaluate the JAK inhibitory effects. Among these JAK1 inhibitors, the compound 23a showed an IC 50 level of 72 nM, as well as being selective against other JAKs by 12 times or more: the results of molecular docking studies suggested that the high JAK1 selectivity resulted from a key interaction between the iodine atom of compound 23a and His-885 of hJAK1., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Glipizide is an N -sulfonylurea compound used in the treatment of hyperglycemia in patients with type 2 diabetes mellitus. In the present study, DFT-based computational methods and molecular docking studies have been performed to systematically evaluate the radical scavenger behavior of the title molecule. Structural characteristics such as molecular descriptors, frontier molecular orbitals, molecular potential mapping, and Mulliken charge population have been investigated. Thermodynamic parameters like proton affinity (PA), ionization potential (IP), bond dissociation energy (BDE), electron transfer enthalpy (ETE), and proton dissociation enthalpy (PDE) related to three antiradical mechanisms namely hydrogen atom transfer (HAT), sequential electron transfer proton transfer (SETPT) and sequential proton loss electron transfer (SPLET) have been studied. Also, molecular docking studies have been carried out to have a theoretical understanding of the molecular mechanism and for the elucidation of binding mode/modes of a compound targeted through non-covalent interactions. The obtained results are of great significance in better understanding the reaction mechanism of the title molecule and opens a new perspective for the design of potent antioxidant agents.

Widely consumed worldwide, Nigella sativa (NS) is a medicinal herb commonly used in various alternative medicine systems, such as Unani and Tibb, Ayurveda, and Siddha. Recommended for regular use in Tibb-e-Nabwi (Prophetic Medicine), NS is considered one of the most notable forms of healing medicine in Islamic literature. Thymoquinone (TQ), the main component of the essential oil of NS, has been reported to have many properties, such as antioxidant, anti-inflammatory, antiviral, and antineoplastic. Its chemical structure indicates antiviral potential against many viruses, including the hepatitis C virus, human immunodeficiency virus, and other coronavirus diseases. Interestingly, molecular docking studies have demonstrated that TQ can potentially inhibit the development of the coronavirus disease 2019 (COVID-19) by binding to the receptor site on the transmembrane serine protease 2 (the activator enzyme that attaches the virus to the cell). In addition, TQ has been shown to be effective against cancer cells due to its inhibitory effect by binding to the different regions of MDM2, according to the proposed molecular docking study. Detailed in this review is the origin of TQ, its significance in alternative medicine, pharmacological value, potential as a cancer antiproliferative agent, use against the coronavirus disease 2019 (COVID-19) and for treatment of other diseases., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

3-(5-(1 H -imidazol-1-yl) pent-1-en-1-yl)-9-ethyl-9 H -carbazole called as compound 1 was synthesized and characterized by proton and carbon-13 nuclear magnetic resonance ( 1 H- and 13 C- NMR) and Fourier transform infrared (FTIR) spectroscopic methods. Density Functional Theory/Becke, 3-parameter (DFT/B3LYP), for compound 1 were performed with 6-311++G(d,p) method. Optimized geometry, frontier molecular orbitals (HOMO; highest occupied molecular orbital; LUMO: lowest unoccupied molecular orbital), IR and NMR parameters of compound 1 were obtained. The evaluations reveal that the calculation results support the experimental results. In addition, the antimicrobial (a microwell dilution method) and antioxidant activities (2,2-Diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonate) (ABTS) ferric ion reducing antioxidant power (FRAP) of compound 1 were evaluated. According to the results obtained, it showed higher antimicrobial activity (Minimal inhibition concentration (MIC): 78.12 µg/mL) against B. subtilis subsp. Spizizenii . Morever, molecular docking studies were carried out to investigate the interactions of an antimicrobial agent on some important enzymes played important roles in nucleic acid (Deoxyribo nucleic acid (DNA) synthesis, cell wall synthesis, protein synthesis, and metabolism etc. The compound 1 was strongly bound to tyrosyl-tRNA synthetase enzyme (binding energy: -11.18 and K i : 6.37 nM) and Beta-Ketoacyl-Acp Synthase III enzyme (binding energy: -10.29 and K i : 28.47 nM).Communicated by Ramaswamy H. Sarma.

A new set of 4,6,7,8-tetrahydroquinolin-5(1H)-ones were designed as cytotoxic agents against breast cancer cell line (MCF-7) and synthesised under ultrasonic irradiation using chitosan decorated copper nanoparticles (CS/CuNPs) catalyst. The new compounds 4b , 4j , 4k , and 4e exhibited the most potent cytotoxic activity of IC 50 values (0.002 - 0.004 µM) comparing to Staurosporine of IC 50 ; 0.005 μM. The latter derivatives exhibited a promising safety profile against the normal human WI38 cells of IC 50 range 0.0149 - 0.048 µM. Furthermore, the most promising cytotoxic compounds 4b , 4j were evaluated as multi-targeting agents against the RTK protein kinases; EGFR, HER-2, PDGFR-β, and VEGFR-2. Compound 4j showed promising inhibitory activity against HER-2 and PDGFR-β of IC 50 values 0.17 × 10 -3 , 0.07 × 10 -3  µM in comparison with the reference drug sorafenib of IC 50 ; 0.28 × 10 -3 , 0.13 × 10 -3  µM, respectively. In addition, 4j induced apoptotic effect and cell cycle arrest at G2/M phase preventing the mitotic cycle in MCF-7 cells.

N-heterocyclic carbene (NHC) adducts have shown remarkable biological potential for numerous medical applications. With an aim to improve biological potential of benzimidazolium salts, newer analogues of benzimidazole and their silver complexes were synthesized and characterized. Synthesized salts (L 1 -L 2 ) and silver complexes (C 1 -C 2 ) were confirmed through elemental analysis, UV-visible spectroscopy, FTIR, 1 H NMR & 13 C NMR spectroscopy. The compounds C1 & C2 were found stable in solution form for studied time period when examined spectroscopically and showed optimum lipophilicity when measured for their partition coefficient through flask shake method. Synthesized compounds showed good antimicrobial potential against gram positive bacterial strain S. Aureus with IC 50 2.02±0.12 and 2.11±0.13 µM respectively while 2.11±0.1 and 2.28±0.17 µM against gram negative bacterial strain E. Coli for C1 and C2 respectively. The interaction study of the related compounds with DNA was predicted by molecular docking study, which confirmed that the studied compound C1 (-8.04 kcal/mol) has a higher binding energy than compound C2 (-4.23 kcal/mol); Also, the compound C1 exhibits a better affinity against to DNA than Ethidium bromide (-7.68 kcal/mol) and cisplatin (-6.21 kcal/mol).The claim was practically assured through spectroscopic and viscometeric method which confirmed that compounds have good affinity for DNA with binding constant kb, 5.78×10 4 M -1 and 6.84×10 4 M -1 for C1 and C2 respectively., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

In this research, a series of novel diosgenin-1,4-quinone hybrids were synthesized and evaluated in antiproliferative assays against three human cancer cell lines (MCF-7, HepG2, and HeLa). Structure-activity relationship analysis revealed that the activities depended on the type of 1,4-quinone moiety. Among them, hybrid 11a exhibited significant cytotoxicity against the HepG2 cell line with a IC 50 of 1.76 μM, which was 35-fold more potent than diosgenin (IC 50 = 43.96 μM). Western blot analysis showed that hybrid 11a upregulated Bax, Cl-caspase-3/9, and Cl-PARP levels, and downregulated Bcl-2 level of HepG2 cell line. Meanwhile, hybrid 11a could increase the generation of intracellular reactive oxygen species. The molecular docking study revealed an interaction between hybrid 11a and NQO1 enzyme. Our present studies suggested that hybrid 11a as a potential substrate for NQO1 enzyme could be a promising anticancer agent for further investigation., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

In the present study, the novel Ag/cellulose nanocrystal (CNC)-doped CeO 2 quantum dots (QDs) with highly efficient catalytic performance were synthesized using one pot co-precipitation technique, which were then applied in the degradation of methylene blue and ciprofloxacin (MBCF) in wastewater. Catalytic activity against MBCF dye was significantly reduced (99.3%) for (4%) Ag dopant concentration in acidic medium. For Ag/CNC-doped CeO 2 vast inhibition domain of G-ve was significantly confirmed as (5.25-11.70 mm) and (7.15-13.60 mm), while medium- to high-concentration of CNC levels were calculated for G + ve (0.95 nm, 1.65 mm), respectively. Overall, (4%) Ag/CNC-doped CeO 2 revealed significant antimicrobial activity against G-ve relative to G + ve at both concentrations, respectively. Furthermore, in silico molecular docking studies were performed against selected enzyme targets dihydrofolate reductase (DHFR), dihydropteroate synthase (DHPS), and DNA gyrase belonging to folate and nucleic acid biosynthetic pathway, respectively to rationalize possible mechanism behind bactericidal potential of CNC-CeO 2 and Ag/CNC-CeO 2 ., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

In 2020, the world tried to combat the corona virus (COVID-19) pandemic. A proven treatment method specific to Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is still not found. In this study, seven new antiviral compounds were designed for COVID-19 treatment. The ability of these compounds to inhibit COVID-19's RNA processing was calculated by the molecular docking study. It has been observed that the compounds can have high binding affinities especially against NSP12 (between -9.06 and -8.00 kcal/mol). The molecular dynamics simulation of NSP12-ZG 7 complex proved the stability of interaction. The synthesis of two most active molecules was performed by one-pot reaction and characterized by FT-IR, 1 H-NMR, 13 C-NMR, and mass spectroscopy. The compounds presented with their synthesis are inhibitory core structures against SARS-CoV-2 infection., Competing Interests: CONFLICT OF INTEREST: none declared, (Copyright © 2021 The Author(s).)

New pregnene analogs of N-hydroxamic acid 6, imino-propane hydrazides 7 and 8 as well as the aryl amides 9-11, oxadiazole, pyrazole and sulfinyl analogs 13-15, via the hydrazide analog 5 of methyl ((5-pregnen-3β,17β-diol-15α-yl)thio)propanoate (4) were synthesized. The in vitro cytotoxic activities of selected synthesized steroids against two human prostate cancer cell lines (PC-3, and LNCaP-AI) were evaluated by MTT assay. Compound 10 was the most active cytotoxic agent among these steroids against PC-3 and LNCaP-AI cell lines with inhibition of 96.2%, and 93.6% at concentration levels of 10.0 μM and 91.8%, and of 79.8% at concentration of 1.0 μM, respectively. Molecular docking study of 10 showed a hydrogen bonding with the amino acid Asn705 residue of the receptor 1E3G, together with hydrophobic interactions. Therefore, compound 10 can be considered as a promising anticancer agent due to its potent cytotoxic activity.

Herein, a series of novel hybrid sulfaguanidine moieties, bearing 2-cyanoacrylamide 2a - d , pyridine-2-one 3 - 10 , and 2-imino-2 H -chromene-3-carboxamide 11 , 12 derivatives, were synthesized, and their structure confirmed by spectral data and elemental analysis. All the synthesized compounds showed moderate to good antimicrobial activity against eight pathogens. The most promising six derivatives, 2a , 2b , 2d , 3a , 8 , and 11 , revealed to be best in inhibiting bacterial and fungal growth, thus showing bactericidal and fungicidal activity. These derivatives exhibited moderate to potent inhibition against DNA gyrase and DHFR enzymes, with three derivatives 2d , 3a , and 2a demonstrating inhibition of DNA gyrase, with IC 50 values of 18.17-23.87 µM, and of DHFR, with IC 50 values of 4.33-5.54 µM; their potency is near to that of the positive controls. Further, the six derivatives exhibited immunomodulatory potential and three derivatives, 2d , 8 , and 11 , were selected for further study and displayed an increase in spleen and thymus weight and enhanced the activation of CD4 + and CD8 + T lymphocytes. Finally, molecular docking and some AMED studies were performed.