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A series of thiadiazole derivatives were designed and synthesized as dual inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) for the treatment of Alzheimer's disease (AD). Furthermore, the compounds were assayed for their inhibitory activity to AChE and BuChE in vitro, and the results indicated that most of the compounds had moderate inhibitory activity to AChE and BuChE. Among them, compound 11 u showed the best inhibitory activity against AChE and BuChE (eeAChE, IC50=2.73 μM; eqBuChE, IC50=0.65 μM), which showed approximately 2‐fold more activity against AChE enzyme than galantamine and approximately 28‐fold more activity against BuChE enzyme than galantamine. In addition, molecular docking studies have shown that compound 11 u could bind to the catalytic active site (CAS) and peripheral anion site (PAS) of AChE and BuChE. Among them, compound 11 u combined with BuChE and exhibited a mixed inhibition pattern consistent with enzyme kinetics studies. The interaction's stability of 11 u‐AChE/BuChE were also assessed using a conventional atomistic 100 ns dynamics simulation study, which revealed the conformational stability of representative compound 11 u in the cavity of the AChE/BuChE. Moreover, the molecular properties of all compounds were predicted by online through the SwissADME, and the best active compound 11 u matched the properties of most orally administered drugs. All these suggested that 11 u could be considered as a lead compound for the development of drugs for AD. [ABSTRACT FROM AUTHOR]

Objective: To synthesize bis-Schiff bases bearing thiobarbituric acid and to screen their anti-urease inhibitory potential. Methods: In this study, 1,3-dimethylbarbituric acid derivatives were synthesized by a four-step process. Using K2CO3, 2,4-dihydroxy benzaldehyde and chloro ethyl acetate were esterified in DMF in the first step under reflux condition. The reaction was then carried out by combining the esterified aldehyde with 1,3-dimethylbarbituric acid at room temperature for about an 1 h. Hydrazine hydrate was then mixed with compound (II) in ethanol solvent with acetic acid acting as catalyst. Finally, substituted aromatic aldehydes were treated with bis-hydrazide (III) using ethanol and acetic acid as a catalyst. Results: The newly synthesized compounds were screened for their urease inhibition (in vitro). Four analogs, including (IIIj) (IC50 = 15.22 ± 0.49 μM), (IIIg) (IC50 = 16.05 ± 0.16 μM), (IIIa) (IC50 = 16.29 ± 0.73 μM), and (IIIb) (IC50 = 21.17 ± 0.21 μM) were found most powerful inhibitors than standard thiourea (IC50 = 22.80 ± 2.20 μM). The urease inhibition was also seen in compound (IIIi), (IIIc), (IIIh), (IIIe), (IIId), and (IIIf) however it was less from standard. The structure stability and chemical reactivity of the compounds were checked by density functional theory (DFT) method. Furthermore, the molecular docking simulation was performed to check the protein (urease) and ligand interactions and binding affinities by using AutoDock Vina. Conclusions: The synthesized derivatives attributed temendous potential against urease enzyme. Compound (IIIj) was found as the most potent anti-urease agent. Additional research including taxicological and in vivo is necessary to know the safety, effectivness and mechanism of action of these potent molecules. [ABSTRACT FROM AUTHOR]

A series of 8-(piperazin-1-yl)imidazo[1,2-a]pyrazine derivatives were designed and synthesized as acetylcholinesterase inhibitors (AChEIs) and antioxidants for the treatment of Alzheimer's disease (AD). Moreover, the biological evaluation results demonstrated that these synthesized compounds exhibited moderate inhibitory activities toward acetylcholinesterase (AChE) and radical scavenging activities. Among them, compound 17r was the most potent AChE inhibitor with an IC50 value of 0.47 μM and moderate inhibitory activity against butyrylcholinesterase (BuChE) (IC50 = 11.02 μM). The selectivity index (SI) value of AChE over BuChE was 23.45, surpassing that of the reference drug galantamine (AChE IC50 = 5.01 μM, BuChE IC50 = 18.46 μM, SI = 3.68). Compound 17o had the best antioxidant activity with an IC50 value of 89.33 μM, which was lower than that of ascorbic acid (IC50 value = 25.70 μM) as the control drug. Furthermore, the results of molecular docking studies indicated that 17r could simultaneously bind to both catalytic active site and peripheral anionic site of AChE, which was consistent with the mixed inhibition pattern shown by enzyme kinetic studies. The interaction's stability of 17r-AChE/BuChE were also assessed using a conventional atomistic 100 ns dynamics simulation study, which revealed the conformational stability of representative compound 17r in the cavity of the AChE. In addition, the molecular properties of all compounds were predicted online through the SwissADME, and the best active compound 17r matched the properties of most orally administered drugs. Based on the biological activity and molecular properties, compound 17r as AChEI was valuable for further development. [ABSTRACT FROM AUTHOR]

Dimers of dipyridothiazines with an m-xylene moiety are presented in terms of a comparative analysis with anticancer active structural analogs containing a lutidine system. The synthesis of new isomeric dimers was described, the structure of which was confirmed by 1H, 13C and 2D NMR, and HR MS spectroscopic methods. The preliminary prediction of the pharmacological profile using the Way2Drug server indicated the anticancer potential of the tested derivatives. In vitro biological activity tests were performed on a normal skin cell line (HaCaT) and five cancer cell lines, including human primary colon cancer (SW480), human metastatic colon cancer (SW620), human breast adenocarcinoma (MDA-MB-231), human lung carcinoma (A-549), and human glioblastoma (LN-229), which indicated low cytotoxic activity. In order to explain the surprisingly low activity, a comparative structural analysis of the tested analogs compared to the dimers with the lutidine system was performed using quantum mechanics and molecular docking in relation to histone deacetylase. Molecular docking indicated the different binding sites of the analyzed dimers, which explained the differences in the activity. [ABSTRACT FROM AUTHOR]

An investigation of the potential ornamental plant Ophiorrhiza chinensis H.S. Lo (Rubiaceae) was conducted, which resulted in the discovery of eight structurally diverse compounds, including two triterpenes, two steroids, two anthraquinones, one alkaloid, and one coumarin. These chemical constituents were isolated by repeated column chromatography and identified by analysis of their NMR spectral data. All of these substances were found in this species for the first time, and four of them were first isolated from the genus Ophiorrhiza. The chemotaxonomic importance of these isolates was discussed, indicating four chemotaxonomic markers for O. chinensis. The tyrosinase inhibitory activity of these isolates was evaluated by a colorimetric method. As a result, six phytochemicals demonstrated moderate tyrosinase inhibitory effects with IC50 values ranging from 25.7 μM to 68.1 μM. Moreover, the binding modes between the active compounds and the mushroom tyrosinase were analyzed preliminarily assisted by molecular docking calculations. This study filled up the knowledge gap of the unreported phytochemical and pharmacological profiles of secondary metabolites from the species O. chinensis. [ABSTRACT FROM AUTHOR]

Green synthesis using L-proline as an organocatalyst is crucial due to its reusability, mild conditions, clean reactions, easy workup, high purity, short reaction times, and high yields. However, existing methods often involve harsh conditions and longer reaction times. In this study, 2-cyano-N'-(2-cyanoacetyl)acetohydrazide (3) was prepared and condensed with various benzaldehyde derivatives to yield 2-cyano-N'-(2-cyano-3-phenylacryloyl)-3-phenylacrylohydrazide derivatives (5a–e, 7a,b) using a grinding technique with moist L-proline. Additionally, three 2-cyano-N'-(2-cyano-3-heterylbut-2-enoyl)-3-heterylbut-2-enehydrazides (9, 11, 13) were synthesized by condensing compound 3 with respective (heteraryl)ketones (8, 10, 12) following the same method. The synthesized compounds were characterized using IR, NMR, and MS spectroscopy. L-proline's reusability was confirmed for up to four cycles without significant yield loss, showcasing the protocol's efficiency and sustainability. The new compounds were screened for anticancer activities against the HCT-116 colon carcinoma cell line using the MTT assay. Molecular docking studies revealed the binding conformations of the most potent compounds to the target protein (PDB ID 6MTU), correlating well with in vitro results. In silico ADMET analysis indicated favorable pharmacokinetic properties, highlighting these novel compounds as promising targeted anti-colon cancer agents. [ABSTRACT FROM AUTHOR]

Poly (1,4-phenylene ether ether sulfone) (PEES) is a commonly used polymer in membrane technology for water treatment applications such as water purification and blood dialyzing in hemodialysis. In this study, PEES was chemically modified by nitration, yielding nitrated Poly (1,4-phenylene ether ether sulfone) (NPEES). Following that, NPEES nanocomposites (NCs) comprise multi-walled carbon nanotubes (MWCNTs), and the process involved the synthesis of reduced graphene oxide-oxidized single-walled carbon nanotubes, abbreviated as reduced (GO-oxSWCNTs). Various characterization techniques were used on the created membranes, such as Fourier-transform infrared spectroscopy (AT-FTIR), X-ray diffraction (XRD), and scanning electron microscopy (SEM) with energy dispersive X-ray (EDX) analysis. All polymer nanocomposites were found to be amorphous, according to the XRD patterns. SEM scans revealed random crater-like features on the surface of NPEES, but MWCNTs and reduced (GO-oxSWCNTs) NCs were distributed evenly on the polymer surface. The primary goal of this study was to evaluate the antimicrobial activity of modified NPEES membranes against two Gram-positive bacteria, Staphylococcus aureus (S. aureus) and Bacillus subtilis (B. subtilis), two Gram-negative bacteria, Pseudomonas aeruginosa (P. aeruginosa) and Escherichia coli (E. coli), and a fungus, Candida albicans (C. albicans). All modified membranes, including NPEES, NPEES/MWCNTs NCs, and NPEES/MWCNTs/reduced (GO-oxSWCNTs) NCs, exhibited antibacterial activity against S. aureus and B. subtilis. Notably, when compared to NPEES/MWCNTs NCs and NPEES/MWCNTs/reduced (GO-oxSWCNTs) NCs, the NPEES membrane had higher antibacterial activity, generating a 12 mm inhibitory zone. Furthermore, molecular docking studies revealed a strong fit of the tested polymer nanocomposites into the DNA gyrase B active site (PDB ID: 4uro), which was consistent with the practical results of their antibacterial activity evaluation. [ABSTRACT FROM AUTHOR]

A series of phthalazine derivatives have been synthesized using green protocol methods under microwave irradiation. This involved subjecting chlorophthalazine to microwave irradiation and employing various reagents, including hydrazine derivatives, primary and secondary amines, and active methylene, to generate the novel phthalazine derivatives. Subsequently, a comparison was made between the yield percentage and reaction time of the resulting products obtained from conventional methods and those obtained through microwave irradiation. The structures of all new compounds were confirmed by physical properties and spectral analysis. The phthalazine compounds demonstrated significant anticancer activity against three cancer cell lines and showed promising selectivity when compared with doxorubicin. Compound 6 exhibited the best anticancer activity, with IC50 1.739 µM, 0.384 µM, and 1.52 µM against MCF7, HCT116, and HepG2 cell lines, respectively. The docking results confirmed that the drugs exert their activity by inhibiting PARP-1. The binding scores were in accordance with the experimental IC50, with compound 6 exhibiting the best binding score and retaining the essential binding interactions with the active site. The results of our computational research have revealed that our phthalazine compounds possess a unique structure that effectively inhibits PARP-1.

The development of novel compounds is essential for the discovery of new therapeutic chemopharmaceuticals. We have synthesized a new Schiff base ligand through condensation of 3,5-dibromo-2-hydroxybenzaldehyde with cyclohexane-1,2-diamine and its relevant transition metal complexes with Mn, Fe, Co, Ni, Cu and Zn metal ions. The synthesized ligand and the metal complexes have been characterized by elemental analysis, UV–Vis, FT-IR, 1H-NMR, 13C-NMR spectroscopy and ESI mass spectrometry; these studies revealed that ligand is bonded to the metal ion via two phenolic oxygen and two azomethine nitrogen. SEM-EDX with mapping analyses of zinc metal complex also demonstrated needle-shaped morphology with uniform distribution of elements. Schiff base metal complexes have been screened for their in vitro antimicrobial activities against Escherichia coli and Staphylococcus aureus bacteria as well as Candida albicans and Aspergillus niger fungi. Also, molecular docking studies inferred the possible interaction of the metal complexes that have been computed using the molecular mechanic calculations using the HyperChem 8.03 molecular modeling program to confirm that there exists a favorable interaction between biomolecules and metal complex. The anticancer tests for MCF-7 breast cancer cell lines conducted with Zn (II) metal complex demonstrated its synergistic effect, exemplifying its involvement in stronger anticancer action, and implementing a higher inhibitory efficiency of the IC50 value of 86.68 ± 0.72 μg/ml for MCF-7 cell. As a result, the current study recognizes the potential of the newly synthesized Schiff base-derived complexes as a preclinical therapeutic agent. [ABSTRACT FROM AUTHOR]

Herein, a novel series of 1,5‐disubstituted‐1,2,3‐triazolines containing 1‐(4‐chlorobenzhydryl) piperazine moiety (8–18) were synthesised and evaluated for their anticancer activity across eight human tumor cell lines. Remarkably, compound 11 substituted with 3‐acetylphenyl group was the most potent anticancer agent against three selected human cancer cell lines (HL‐60, Z138, and DND‐41) with IC50 values of 16.80, 18.50, and 19.20 μM, respectively. In contrast, analogue 10 demonstrated activity against HL‐60, Z138, and DND‐41 cell lines, with IC50 values of 19.90, 18.00, and 18.50 μM, respectively. Moreover, derivative 13 substituted with 4‐bromophenyl moiety displayed activity with IC50=19.90 μM against the DND‐41 cell line. However, all analogues showed IC50 values ranging from 22.95 to 58.45 μM when tested against other investigated cancer cell lines. These findings suggest that derivative 11 holds promise as a potential candidate for synthesizing novel anticancer agents. Furthermore, compounds 8–18 were screened for their antioxidant activity. Molecular docking studies of compound 11 on crystal structures of two proteins, CDK2/cyclin A2 (PDB: 7B7S) and kinase Akt1 PKB alpha (PDB: 4GV1) have been studied. [ABSTRACT FROM AUTHOR]

Abstract 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 K2CO3 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, 1H, and 13C-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 IC50 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.

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 K2CO3 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, 1H, and 13C-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 IC50 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

A series of 8‐(piperazin‐1‐yl) imidazo [1,2‐a] pyrazine derivatives were designed and synthesized as acetylcholinesterase inhibitors (AChEIs) and antioxidants for the treatment of Alzheimer's disease (AD). Moreover, the biological evaluation results demonstrated that these synthesized compounds exhibited moderate inhibitory activities toward acetylcholinesterase (AChE) and radical scavenging activities. Among them, the compound with the strongest inhibitory activity against AChE had an IC50 value of 0.55 μM, which was higher than that of galantamine as the reference compound (IC50 value=5.01 μM). The compound with the strongest antioxidant activity had an IC50 value of 57.94 μM, which was lower than that of the ascorbic acid (IC50 value=25.70 μM) as the control drug. Furthermore, the results of molecular docking studies indicated that the compound could simultaneously bind to both catalytic active site (CAS) and peripheral anionic site (PAS) of AChE, which was consistent with the mixed inhibition pattern shown by enzyme kinetic studies. The interaction's stability was also assessed using a conventional atomistic 100 ns dynamics simulation study, which revealed the conformational stability of representative compound in the cavity of the AChE. In addition, the molecular properties of all compounds were predicted online through the SwissADME, and most compounds matched the properties of most orally administered drugs. Based on the biological activity and molecular properties, 8‐(piperazin‐1‐yl) imidazo[1,2‐a] pyrazine derivatives as AChEI were valuable for further development. [ABSTRACT FROM AUTHOR]

A new copper(II) complex with 2-amino-6-methylpyrimidin-4-(1H)-one, [Cu(C5H7N3O)4](NO3)2·H2O (Cupyrim), has been synthesized and studied by X-ray diffraction, elemental analysis and FT-IR spectroscopy. The Cu(II) is four-coordinate in a square planar geometry by four nitrogen atoms of the four organic ligands. Hirshfeld Surface Analysis was conducted to understand crystalline packing. Overall, the structure is maintained by metal coordination as well as strong and weak (C,N)–H···O hydrogen bonds and C–H...π interactions. The IR spectrum primary peaks have been assigned to the vibration modes of the ligand functional groups. An investigation of the inhibitory properties of Cupyrim toward "Cyclin-dependent Kinase 2" (CdK2) and "inducible nitric oxide synthase" (iNOS) proteins was aided by molecular docking research. According to molecular docking, Cupyrim exhibits promising inhibitory efficacy against Parkinson's, schizophrenia, and Alzheimer's disorders. The temperature dependence of the real and imaginary part of the dielectric permittivity was analyzed with the Cole-Cole formalism as well as DSC diagrams from 45-147 °C. [ABSTRACT FROM AUTHOR]

ERK1 and ERK2 are ubiquitous, evolutionarily conserved serine threonine kinases that govern cellular signalling in both normal and pathological situations. ERK expression is essential for development and their hyper activation plays a significant role in the progression and development of cancer. Using a hybridization method, a series of new thiadiazole-triazole derivatives were synthesised and characterised using spectral data. These compounds were evaluated for anti-cancer activity against HT-1080 and A-549 cells using the MTT assay. All of the compounds suppressed cells well, and the findings were comparable to those of the standard doxorubicin. Compounds with substituted phenyl and 4-methoxyphenyl groups displayed enhanced anti-proliferative activity. The binding interactions of the compounds were further analysed using the molecular docking approach. Induced significant binding interactions with the ERK protein. Hence, these molecules can serve as promising for developing efficient drugs targeting ERK. [ABSTRACT FROM AUTHOR]

A new Cu(II) complex with the monodentate ligand 2,6-dimethylpyrimidin-4-(1 H)-one, [CuCl(C6H8N2O)2H2O]Cl.3H2O, was synthesized and characterized by single crystal X-ray diffraction, elemental analysis, and IR spectroscopy along with detailed theoretical studies based on density functional theory (DFT) at the B3LYP-D3(BJ)/Def2-SVP method. In the structural arrangement of the title compound, the different chemical entities are connected to each other via O–H....O, O–H...Cl, and N–H...O hydrogen bonds to form a three-dimensional network as revealed by the Hirshfeld intramolecular and surface analysis. Infrared spectroscopy analysis confirms the presence of a peak at 2344 cm− 1 which is assigned to N = C stretching vibrations while those at 1670 and 1622 cm− 1 respectively correspond to the C = C asymmetric stretching vibrations. The in-silico investigation of the anti-fibrotic potential of the title compound was carried out molecular docking with the 4FUX and 4FV3 receptors alongside PIRF which is a standard show that the title compound performed better in terms of H-bond interaction as well as binding affinity. Furthermore, the presence of 3 conventional H-bond interactions in the 4FUX-Complex interaction compared to 1 for the 4FV3-PIRF makes it very obvious that the bioactivity of this complex for fibrosis is greater than that of PIRF within the limits of available data as contained in this study. [ABSTRACT FROM AUTHOR]

Four copper (II) complexes [Cu(L1)2] (1), [Cu(L2)2] (2), [Cu(L3)2] (3) and [Cu(L4)2] (4) with azo linked O,O donar ligands viz 2-hydroxy-5 (phenyldiazenyl)benzaldehyde (HL1), 1-(2-hydroxy-5-(phenyldiazenyl)phenyl)ethanone (HL2), 2-Hydroxy-5-p-tolylazo-benzaldehyde (HL3), 1-(2-Hydroxy-5-p-tolylazo-phenyl)-ethanone (HL4) have been prepared and characterized by different spectroscopy methods and published earlier by our research group. We investigated the interaction of Human Serum Albumin (HSA) with complexes 1–4 under physiological condition in phosphate buffer solution at pH 7.4 using various spectroscopic techniques. The fluorescence titration spectrum disclosed that the complex 1–4 quench the intrinsic fluorescence of HSA robustly through a static quenching mechanism. Binding constants (Kb) and the number of binding sites (n ≈ 1) were evaluated using modified Stern–Volmer equations. Binding constants were found to be 1.9, 6.6, 0.99 and 1.2x 105 (M−1) for complex 1, 2, 3 and 4 respectively. The CD spectra of free HSA and HSA with complexes 1–4 showed that the complexes have negligibleimpact on the secondary structure of HSA as theyremain helical even after the addition of complexes. Molecular docking study was performed to analyse the binding mode of complexes 1-4with HSA. Docking study revealed that hydrophobic and Vander waals interactions were considered to be the main interaction forces involved in the binding of HSA with complexes 1–4.

The investigation employed cyclic voltammetry (CV) assays to assess the scavenging efficacy of two recently developed compounds, namely meso-tetramethophenyl-porphyrin TPPH2(o-methyl) and meso-tetrabiphenyl-porphyrin (TbiPPH2), against the superoxide anion radical ( ). The IC50 values derived from the CV assays indicated significant scavenging activity for both compounds, with TbPPH2 exhibiting superior potency (85.79 ± 0.11 µg ml-1) compared to the standard antioxidant alpha-tocopherol (353.27 ± 3.21 µg ml-1). Additionally, molecular docking simulations elucidated the interaction of the investigated compounds with specific amino acid residues of glutathione reductase through hydrogen bonding and hydrophobic interactions. The in vitro and in silico results were concordant, highlighting TbiPPH2 as the least active compound against glutathione reductase, boasting the highest inhibitory concentration of 0.63 μM and the lowest docking score of -35.36 kJ mol-1, thus positioning it as a promising candidate for antioxidant applications.

An investigation of the potential ornamental plant Ophiorrhiza chinensis H.S. Lo (Rubiaceae) was conducted, which resulted in the discovery of eight structurally diverse compounds, including two triterpenes, two steroids, two anthraquinones, one alkaloid, and one coumarin. These chemical constituents were isolated by repeated column chromatography and identified by analysis of their NMR spectral data. All of these substances were found in this species for the first time, and four of them were first isolated from the genus Ophiorrhiza. The chemotaxonomic importance of these isolates was discussed, indicating four chemotaxonomic markers for O. chinensis. The tyrosinase inhibitory activity of these isolates was evaluated by a colorimetric method. As a result, six phytochemicals demonstrated moderate tyrosinase inhibitory effects with IC50 values ranging from 25.7 μM to 68.1 μM. Moreover, the binding modes between the active compounds and the mushroom tyrosinase were analyzed preliminarily assisted by molecular docking calculations. This study filled up the knowledge gap of the unreported phytochemical and pharmacological profiles of secondary metabolites from the species O. chinensis.

Dimers of dipyridothiazines with an m-xylene moiety are presented in terms of a comparative analysis with anticancer active structural analogs containing a lutidine system. The synthesis of new isomeric dimers was described, the structure of which was confirmed by 1H, 13C and 2D NMR, and HR MS spectroscopic methods. The preliminary prediction of the pharmacological profile using the Way2Drug server indicated the anticancer potential of the tested derivatives. In vitro biological activity tests were performed on a normal skin cell line (HaCaT) and five cancer cell lines, including human primary colon cancer (SW480), human metastatic colon cancer (SW620), human breast adenocarcinoma (MDA-MB-231), human lung carcinoma (A-549), and human glioblastoma (LN-229), which indicated low cytotoxic activity. In order to explain the surprisingly low activity, a comparative structural analysis of the tested analogs compared to the dimers with the lutidine system was performed using quantum mechanics and molecular docking in relation to histone deacetylase. Molecular docking indicated the different binding sites of the analyzed dimers, which explained the differences in the activity.

Six new thiosemicarbazones were prepared and structurally characterized by elemental analysis, NMR and IR spectra and single-crystal X-ray diffraction. The compounds were evaluated for their Jack bean urease inhibitory activities. Among the compounds, those with hydroxyl and chloro substituent groups have effective activity with IC50 values of 1.8-12.7 µmol L-1. Docking simulations were performed to insert the molecules of the compounds into the active urease site determined by the crystal structure to determine their probable binding modes. [ABSTRACT FROM AUTHOR]

Basil (Ocimum basilicum L) is a plant that belongs to the Lamiaceae family and is known for its pharmacological and therapeutic properties, as it is rich in active biological substances, which endow it with antioxidant and anti-inflammatory activities. Many people from all over the world use basil in traditional medicine, including North African countries, especially Algeria, which they use to treat many organic and infectious diseases. On the other hand, according to scientific reports, the O. basilicum plant contains most of the major and biologically active molecules such as flavonoids, phenols, tannins, steroids, glycosides, and reduced sugars. Pharmacological studies also indicate that the plant has antioxidant, anti-inflammatory, analgesic and antibacterial activities. In silico tools, a compound's ability to block a receptor can be successfully studied by combining many in silico approaches. There have been reports of natural chemicals of O. basilicum having anticancer action. In conclusion, O. basilicum may be one of the best sources of plant medicines that can be used to treat many acute and chronic diseases. [ABSTRACT FROM AUTHOR]

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.

Green synthesis using L-proline as an organocatalyst is crucial due to its reusability, mild conditions, clean reactions, easy workup, high purity, short reaction times, and high yields. However, existing methods often involve harsh conditions and longer reaction times. In this study, 2-cyano-N’-(2-cyanoacetyl)acetohydrazide (3) was prepared and condensed with various benzaldehyde derivatives to yield 2-cyano-N’-(2-cyano-3-phenylacryloyl)-3-phenylacrylohydrazide derivatives (5a–e, 7a,b) using a grinding technique with moist L-proline. Additionally, three 2-cyano-N’-(2-cyano-3-heterylbut-2-enoyl)-3-heterylbut-2-enehydrazides (9, 11, 13) were synthesized by condensing compound 3 with respective (heteraryl)ketones (8, 10, 12) following the same method. The synthesized compounds were characterized using IR, NMR, and MS spectroscopy. L-proline’s reusability was confirmed for up to four cycles without significant yield loss, showcasing the protocol’s efficiency and sustainability. The new compounds were screened for anticancer activities against the HCT-116 colon carcinoma cell line using the MTT assay. Molecular docking studies revealed the binding conformations of the most potent compounds to the target protein (PDB ID 6MTU), correlating well with in vitro results. In silico ADMET analysis indicated favorable pharmacokinetic properties, highlighting these novel compounds as promising targeted anti-colon cancer agents.

Current study was conducted to assess the effectiveness of the polyphenol trans-ferulic acid (TFA) as an antiemetic agent using in vivo and in silico methods. To evaluate this, we induced emesis in 3-day-old chicks through the oral administration of copper sulfate (CuSO4·5H2O) at a dose of 50 mg/kg. To ascertain the potential antiemetic mechanism of TFA, we employed various reference drugs such as domperidone (6 mg/kg), ondansetron (5 mg/kg), and hyoscine (21 mg/kg) as positive control groups, while the vehicle acted as a negative control group. TFA was administered orally at the doses of 25, 50 and 100 mg/kg body weight. Both the TFA and reference drug provided alone or in combined groups to assess their synergistic or antagonistic activity on the chicks. Molecular docking of TFA and the selected reference drugs was conducted against 5HT3, D2, H1, NK1, and mAChRs (M1-M5) receptors for determining binding affinity to the receptors. Active binding sites and drug-receptor interactions were predicted with the aid of various computational tools. Various pharmacokinetic features and drug-likeness of all the selected ligands were determined through the SwissADME online server. The results suggest that TFA diminishes the mean number of retches and enhances latency in the chicks at lower doses. In the combined drug therapy, TFA exhibited better antiemetic effects with ondansetron and hyoscine. In silico ADME proposed that TFA retains preferable drug-likeness and better pharmacokinetic properties to be a reliable lead. Additionally, TFA revealed the elevated binding affinity against mAChRs and the ligand (TFA) expressed the highest binding affinity (−7 kcal/mol) with the M5 receptor (6OL9). In conclusion, TFA demonstrated mild antiemetic effects in chicks, possibly through the mAChRs interaction pathway.

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 (IC50 = 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 IC50 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. [ABSTRACT FROM AUTHOR]

The activation of Hh pathway demonstrates therapeutic potential for many diseases. Smo is the main target for the development of Hh pathway modulators. However, compared with Smo antagonist, the development of Smo agonists is lagging behind. Based on our previous work, a series of vismodegib derivatives were designed and synthesized, and their potential to activate the Hh pathway were evaluated via determining the up-regulation of known pathway target genes Gli1, whcih revealed that many target compounds could activate the Hh pathway. XH-16 and XH-17, with the strongest agonistic effect, could upregulate the expression of Gli1 by more than 50% at a concentration of 10 μM. In vitro cytotoxicity against A549 and the MDA-MB-231 cells was evaluated and the results revealed that XH-16 and XH-17 did not exhibit cytotoxicity at a concentration of 50 μM. Molecular docking results confirmed that XH-16 and XH-17 could bind to Smo indicating that their agonistic effect on the Hh pathway may be due to the activation of Smo. XH-16 and XH-17 with novel molecular scaffold could be used as a lead compound for the development of Smo agonists. Moreover, the research process was introduced in a medicinal chemistry experimental course to assist undergraduates in understanding the core of medicinal chemistry and building capabilities for independently carrying out a medicinal chemistry project. And the teaching practice experiences were summed up to provide suggestions for the development of exploratory experimental course. [ABSTRACT FROM AUTHOR]

Bromo, Nitro, Dichloro, Amino Substituted Carboxylate Derivatives of Thiophenes[a=2-bromo, b=4-nitro,d=2,4-dichloro, f=3-amino] have been synthesized by using Gewald reaction under mild reaction conditions. The obtained products were analyzed by IR, 1HNMR, 13C NMR, and Mass spectroscopy techniques. These compounds have explored binding affinity against GlcN-6-P synthesis. Taking into account factors such as docking energy, binding energy, inhibition constant and intermolecular energy, molecular docking determined the optimal potential conformations for the compounds obtained. Synthesized compounds NR3 and NR6 exhibited the lowest binding energy compared to the standard fluconazole. In vitro, biological studies such as antibacterial, antifungal, antidiabetic, and anti-inflammatory properties were investigated for the synthesized compounds NR3, NR4, NR6, and NR8. The compounds showed significant antibacterial, antifungal, antidiabetic, and anti-inflammatory activities. The results showed that almost all synthesized compounds were more potent against Bacillus cereus and Candida albicans than the standard drugs Ciprofloxacin and Itraconazole. [ABSTRACT FROM AUTHOR]

Four new fluoro-containing hydrazones were synthesized from 4-fluorobenzaldehyde with chloro- and nitro-substituted benzohydrazides. They are 3-chloro-N'-(4-fluorobenzylidene)benzohydrazide (1), 2-chloro-N'-(4-fluorobenzylidene) benzohydrazide (2), N'-(4-fluorobenzylidene)-4-nitrobenzohydrazide (3), and N'-(4-fluorobenzylidene)-3-nitrobenzohydrazide (4). The compounds have been characterized by IR and 1H NMR spectroscopy, as well as X-ray single crystal determination. Xanthine oxidase (XO) inhibitory activity indicated that the nitro substituted compounds 3 and 4 have effective activity. Docking simulation was performed to insert the compounds into the crystal structure of xanthine oxidase at the active site to investigate the probable binding modes. [ABSTRACT FROM AUTHOR]

The azo ligand obtained from the diazotization reaction of 2-aminobenzothiazole and 4-nitroaniline yielded a novel series of complexes with Co(II), Ni(II), Cu(II), and Zn(II) ions. The complexes were investigated using spectral techniques such as UV-Vis, FT-IR, 1H and 13C NMR spectroscopic analyses, LC-MS and atomic absorption spectrometry, electrical conductivity, and magnetic susceptibility. The molar ratio of the synthesized compounds was determined using the ligand exchange ratio, which revealed the metal-ligand ratios in the isolated complexes were 1:2. The synthesized complexes were tested for antimicrobial activity against S. aureus, E. coli, C. albicans, and C. tropicalis bacterial species. Additionally, their binding affinities were predicted using molecular docking analysis, and their pharmacokinetic and drug-likeness properties were evaluated. [ABSTRACT FROM AUTHOR]

In this study, a new (E)-3-(3-bromo-4-methoxyphenyl)-1-(4-(methylthio)phenyl)prop-2-en-1-one was synthesized by a condensation method. It has been characterized using FT-IR, UV-Vis spectra, and NMR spectra. Furthermore, the title compound was subjected to DFT analysis to observe its molecular structure and vibrational wavenumbers using the B3LYP/6-311G(d,p) approach. The total energy distribution (TED) method was used for complete vibrational analysis. Proton and carbon nuclear magnetic resonance (NMR) chemical shifts of the target compound were calculated theoretically by the gauge independent atomic orbital (GIAO) method and compared with experimental data. For the title molecule, the geometrical parameters provided the best agreement with experimental ones. The HOMO-LUMO energy gap, chemical reactivity parameters, Mulliken atomic charge, and molecular electrostatic potential (MEP) are also studied. The results obtained from the DFT analysis were in good agreement with the experimental data. The synthesized compound was also used in molecular docking studies to understand its biological activity. [ABSTRACT FROM AUTHOR]

New Delhi Metallo-β-lactamase (NDM-1) is an enzyme that hydrolyses a wide range of β-lactam antibiotics, including most carbapenems, leading to antimicrobial resistance. The development of a novel NDM-1 inhibitor for use in combination with carbapenems may help to combat drug-resistant pathogens. Twenty compounds were designed based on the structural features of the NDM-1 active site to inhibit bacterial NDM-1 and protect β-lactam antibiotics from enzyme attack. The designed molecules were naphthalene, thiazole, and sulfone derivatives because they could coordinate with the zinc ions and form hydrophobic contracts with the enzyme's active site. A molecular docking protocol was used to identify potential inhibitor(s) of the NDM-1 target protein. Furthermore, drug-likeness and pharmacokinetic properties of the designed molecules were predicted. Three compounds with the more negative ΔGbinding results were selected for further investigation using molecular dynamic (MD) simulations. T016 had a significantly more negative binding free energy than the positive control and other designed molecules, had stable MD simulations (Root-mean-square deviation < 0.5 Å), passed Lipinski's rule of five, and had favourable physicochemical and pharmacokinetic properties. The findings can be used to inform the synthesis and in vitro testing of the selected molecules. [ABSTRACT FROM AUTHOR]

4-((4-(1-benzyl-2-methyl-4-nitro-1H-imidazole-5-yl)piperazine-1-yl)methyl)-1-substituted-1H-1,2,3-triazole motifs are designed and synthesized via click chemistry. The reaction of 1-(N1-benzyl- 2-methyl-4-nitro-1H-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 1H NMR, 13C 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 IC50 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.

A new series of indole-oxindole clubbed 1,2,3-triazole hybrids 5(a–o) was thoughtfully designed and synthesized via Cu-catalysed azide-alkyne cycloaddition (CuAAC) click reaction while taking into account the varied medicinal activities of indole, oxindole, and 1,2,3-triazole derivatives. By employing the broth micro dilution method, the antimicrobial potential of each synthesized hybrid molecule was examined against three gram-negative (Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumonia), three gram-positive (Bacillus subtilis, Staphylococcus aureus, and Streptococcus pyogenes), and two fungal strains (Candida albicans and Aspergillus niger). Compound 5e was shown to be the best antibacterial agent with a minimum inhibitory concentration (MIC) of 25 μg/mL against Escherichia coli among all the synthetics. Molecular docking study also streamlined the plausible interactions of compound 5e with the active site of DNA gyrase. The SwissADME webserver analysis revealed that the majority of synthetic compounds adhere to the principles of drug-likeness. [ABSTRACT FROM AUTHOR]

The ligand namely N-(8-hydroxyquinolin-5-yl)-2,4,6-trimethylbenzene sulfonamide (8HQTBS) and its complexes with transition metals were synthesized using transition metal ions. Prepared ligand and their metal complexes were examined by the study of physicochemical properties, various spectral techniques, and magnetic susceptibility. Octahedral geometry of the transition metal complexes was proposed by spectral studies. The antimicrobial profile of prepared ligands and complexes (In vitro) showed better activity of ligands after metal complexation. Strong binding of transition metal complexes with CT-DNA was observed through the intercalation mechanism. A comparative molecular docking study between bacterial proteins and a DNA helix was performed, and the docking results obtained were in good agreement with the spectroscopic results. Some of the compounds showed good to moderate antimalarial activity. [ABSTRACT FROM AUTHOR]

Background: Cancer is the world's leading cause of death; more than ten million people die from cancer each year. Rate of morbidity and mortality is increasing day by day. As a result, utilizing chemoinformatics techniques, a novel series of Methylenedioxyphenyl linked with 3,4,5-trimethoxyphenyl/2,5-dimethoxyphenyl and pyrimidine has been designed, docked and in-silico predictions of pharmacokinetic, and toxicological parameters. Materials and Methods: A novel class of Methylenedioxyphenyl derivatives was docked by using AutoDock Vina software to reveal the interaction of these derivatives with the active site topoisomerase-II with PBD ID 5GWK. In addition to the above, the ADME studies were performed using Swiss ADME software and the toxicity parameters using the pkCSM online tool. Results: Many derivatives were found to be more active than the standard drug etoposide in docking studies. Binding interaction pattern of selected compounds were studied with the active sites of DNA topoisomerase-II (PBD ID 5GWK) by docking simulation. The results of the screening revealed that compounds B9, B12, B13, B15, B16, B17, B18, B22, and B23 were more active candidates of the series. Conclusion: Molecular docking and ADME/Tox properties of new methylenedioxyphenyl derivatives have been described. As a result, nine compounds from the intended series showed improved docking scores with suitable ADME/Tox properties and satisfactory topo II inhibiting activity, thus these compounds may be the effective inhibitors of topoisomerase IIa enzyme. [ABSTRACT FROM AUTHOR]

Prunus mahaleb L., also known as white mahaleb, and native to the Kurdistan region of Iraq, has significant nutraceutical and therapeutic ingredients. The seeds are rich in conjugated fatty acids with small quantities of cyanogenic glycosides, coumarin derivatives, and flavonoids. The contents of the seeds were extracted with the Soxhlet apparatus using n-hexane and petroleum ether solvents, separately. Gas chromatography-mass spectrometry (GC-MS) was used to recognize the chemical composition of the compounds. The radical scavenging activity was performed for the total extracts from n-hexane and petroleum ether solvents using 2,2-diphenyl-1 picrylhydrazyl (DPPH) assay and compared with quercetin as a positive control. Furthermore, molecular docking was performed for the identified compounds against five enzymes that have main roles in intracellular oxidation. Afterwards, drug-like properties and bioactivity predictions were applied for all compounds using Molinspiration software. The results showed four phthalate derivatives, six saturated fatty acids (SFAs), five monounsaturated fatty acids (MUFAs), and three polyunsaturated fatty acids (PUFAs). The n-hexane extract showed competitive antioxidant activity with quercetin and the in-silico studies suggested a notable antioxidant activity of the seed oil contents with apparent drug-likeness properties. Further studies are required to separate the extracts, then perform in vitro antioxidant activity on the compounds. [ABSTRACT FROM AUTHOR]

Identifying the ways in which drugs interact with DNA is crucial from a pharmacological point of view, and therefore determining the binding mode of tacrine-coumarin derivatives with DNA is key to gaining a fuller understanding of the activity of these compounds. Seven tacrine-coumarin derivatives 1a−1d and 2a−2c have been evaluated for their binding affinity to calf thymus DNA (ctDNA) by a variety of spectroscopic techniques including UV–Vis absorbance, fluorescence and CD spectroscopy. The effect of 1a−1d and 2a−2c on thermal denaturation profiles of ctDNA was also studied. The binding constants for the ctDNA-drug complexes were determined on the basis of spectrophotometric and spectrofluorometric titrations. Evidence has been provided that the tacrine-coumarin hybrid molecules bind to ctDNA through a non-intercalative mode of interaction such as groove binding. For derivatives 1d and 2c molecular docking was performed for two different DNA conformations. The results of preliminary molecular docking show that the most favourable DNA binding mode of these derivatives is non-intercalative. [ABSTRACT FROM AUTHOR]

In this paper, 20 compounds containing bis-(1,2,3 and 1,2,4)-triazole structure were synthesized and their antifungal activities against Candida fungi and Aspergillus niger were analyzed in vitro. Some of the prepared compounds exhibited the most promising activity compared with voriconazole and amphotericin B. Molecular docking studies were performed to for additional substantiation of antifungal activity of these derivatives. So, these compounds are expected to provide new ideas for the development of antifungal drugs. [ABSTRACT FROM AUTHOR]

The ongoing work describes the catalytic evaluation of γ‐Fe2O3@Ag‐S‐CH2‐COOH magnetic nanoparticles utilizing γ‐Fe2O3 obtained from waste iron rust for one‐pot synthesis of 2,3‐dihydroquinazolin‐4(1H)‐ones. As‐prepared γ‐Fe2O3@Ag‐S‐CH2‐COOH nanoparticles were characterized by Fourier transform infrared spectroscopy (FT‐IR), X‐ray diffraction (XRD), scanning electron microscopy (SEM), energy‐dispersive X‐ray spectroscopy (EDX), dynamic light scattering (DLS), transmission electron microscopy (TEM), X‐ray photoelectron spectroscopy (XPS), and Brunauer–Emmett–Teller (BET) technique. The catalytic performance of greener γ‐Fe2O3@Ag‐S‐CH2‐COOH nanoparticles was utilized in the synthesis of 2,3‐dihydroquinazolin‐4(1H)‐ones. The excellent catalytic performance was shown by magnetic nanoparticles in addition to its ease of separation by an external magnet and can be recycled for five consecutive turns without significant loss of catalytic activity. Furthermore, the synthesized 2,3‐dihydroquinazolin‐4(1H)‐ones were confirmed by FT‐IR, 1H, 13C nuclear magnetic resonance (NMR), and mass spectrometry. Moreover, the synthesized 2,3‐dihydroquinazolin‐4(1H)‐ones were evaluated for their anticancer efficiency against the human skin cancer cell line B16F10 along with molecular docking investigation. [ABSTRACT FROM AUTHOR]

The co-localization of the donor and acceptor fluorophores capable of transferring the energy by the Fӧrster mechanism, on the molecular scaffold of amyloid fibrils offers new opportunities not only for refinement of the amyloid detection and structural analysis, but also for designing photonic nanodevices on their basis. The assembly of these systems involves the non-covalent dye-protein interactions which can hardly be characterized in terms of a precise dye location within the fibril structure that is required for fabricating the FRET-based light harvesting systems or photonic nanowires. In view of this, the dye-fibril binding process deserves a detailed in silico study. In the previous molecular docking studies of the FRET donors and acceptors interacting with the insulin model fibrils we considered only one ligand during the simulation procedure. However, the real situation is much more complicated, when the multiple ligands can compete for the same binding site, a direct complexation between the dyes on the fibril scaffold can take place, the spatial distribution of the bound fluorophores can be unfavorable for the energy transfer, etc. In addition, the mutual orientation of the donor and acceptor molecules essentially contribute to the efficiency of the Förster resonance energy transfer (FRET) in the investigated systems. The present study was undertaken to gain molecular docking insight into the binding of the donor (Thioflavin T) and acceptor (Congo Red or a phosphonium dye TDV) fluorophores to the insulin amyloid fibrils using the multiple docking approach. The employed PatcDock and SwissDock webserves provided evidence for the preferable association of all dyes with the fibril grooves. The protein-ligand interaction profiler (PLIP) was employed for analyzing the (InsF + ThT +CR) and (InsF + ThT + TDV) systems. The revealed binding modes and the types of the dye-fibril interactions may be of importance for a more detailed analysis of the FRET process in amyloid systems and may serve as a background for further in silico studies of the cascade FRET on the amyloid fibril scaffold.

Background: Alzheimer's Disease (AD) is a neurodegenerative disorder with progressive impairment of behavioural and cognitive functions and the most common cause of dementia. The pathophysiology of AD is associated with low acetylcholine, accumulation of amyloid beta plaque, and neurofibrillary tangles in the brain. Cinnamomum zeylanicum is known to have many medicinal properties, especially neuroprotective effects. Objective: This research was designed to determine the neuroprotective potential of the phytochemicals C. zeylanicum using an in silico study. Methods: There are 5 phytochemicals compounds of C. zeylanicum used in this study. It's qualified for Lipinski's rules of five and can cross blood brain barrier. The protein targets were AChE, BACE1, and GSK-3. Molecular docking and visualization were performed using Avogadro, AutoDock 4.2 PyMol and Biovia Discovery Studio 2019. Results: In silico results show that the main phytochemical compounds of C. zeylanicum Blume essential oil have great potency as an AD drug. The best interaction model of the compound was shown by trans-cinnamyl acetate and coumaric acid. Although the binding energy of the compounds is lower than AD drugs (donepezil, rivastigmine, galantamine), the binding energy is not much different from rivastigmine and galantamine. Conclusion: The phytochemical compounds of C. zeylanicum Blume essential oil have an effect as a neuroprotective agent for AD and should be investigated in future research. [ABSTRACT FROM AUTHOR]

A couple of series of heterocyclic‐based urea and thiourea derivatives, connected with a hybrid scaffold skeleton containing pyrazole and piperazine ring moieties, were achieved. In this study, a total of fifteen new compounds were synthesized by reacting 1‐(3‐methyl‐1‐phenyl‐1H‐pyrazol‐5‐yl)piperazine hydrochloride with carbamides and thiocarbamides. All the fifteen newly synthesized compound structures were confirmed by 1H & 13C NMR and FTIR spectroscopy, ESI mass spectrometry, CHNS analysis and HPLC chromotograms. Moreover, the structures of N‐allyl‐4‐(3‐methyl‐1‐phenyl‐1H‐pyrazol‐5‐yl)piperazine‐1‐carbothioamide and 4‐(3‐methyl‐1‐phenyl‐1H‐pyrazol‐5‐yl)‐N‐(4‐nitrophenyl)piperazine‐1‐carbothioamide were also confirmed by single‐crystal X‐ray diffraction analysis. Further, as per the objective of this work, all these fifteen newly synthesized compounds were screened for anti‐inflammatory activity. The majority of the compounds displayed moderate‐to‐good anti‐inflammatory activity. The anti‐inflammatory activity study was also correlated with molecular docking studies using the receptor Cyclooxygenase‐2. [ABSTRACT FROM AUTHOR]

A series of new substituted benzimidazole-thiazoles (9a–l) have been designed and synthesized using 2-aminothiazole as a starting material by using molecular hybridization approach. The newly synthesized compounds were characterized by 1H NMR, 13C NMR and HRMS analyses. The compounds (9a–l) were evaluated for their in vitro antitubercular activity against Mtb (MTCC 300) strain. Among the screened compounds 9a, 9b, 9c and 9d have displayed promising antitubercular activity with MIC 7.55, 4.60, 15.39 and 28.38 μg/mL, respectively. All the compounds were further evaluated for their DPPH radical scavenging activity. The compounds 9a, 9b and 9d were exhibited excellent radical scavenging activity. In addition to this, single crystal structure of compound 9a was also studied. Furthermore, the high potency of these molecules was supported by ADME properties prediction as well as molecular docking study to gain an insight into the binding mode and affinity toward mycobacterial InhA. [ABSTRACT FROM AUTHOR]

A set of novel N-methylspiropyrrolidine hybrids have been synthesized regio selectively employing 1,3-dipolar cycloaddition reaction of substituted chalcones with azomethine ylides (work up in situ from isatin and sarcosine). The spiropyrrolidines structures were studied using FT-IR, 1H and 13C NMR spectroscopic data, and was finally confirmed by X-ray diffraction study. Hirshfeld surface analysis was correlated with X-ray diffraction and described different intermolecular contacts. Good antibacterial activity was reported against gram-positive and gram-negative bacterial strains of Bacillus subtillis, Enterococcus faecalis, E. coli, and Pseudomonas aeruginosa. Initially, antibacterial activity of compounds was confirmed by the zone of inhibition. Most of the compounds have shown MIC and MBC in the range between 50-200 µg∕mL against both types of bacteria. Further, for mechanism of action, the tested compounds were checked for the inhibition of an established bacterial drug target, DNA gyrase using in silico approaches. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

In this study, the synthesis of Schiff bases containing substituted thiophene was carried out. The compounds were characterized by Fourier transform infrared (FTIR), 1H and 13C NMR spectroscopy methods. In the study, it was aimed to determine in vitro leishmanicidal activities of five different newly synthesized compounds against standard L. infantum promastigotes by microdilution method. In silico analysis was used to examine the probable interactions between the synthesized compound and the target proteins. [ABSTRACT FROM AUTHOR]