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An innovative class of novel 2-aryl-5-(1-aryl-1H-pyrazol-3-yl)-1,3,4-oxadiazoles 5i–w have been synthesized from ring transformation using L-proline as an organocatalyst. This novel method using organocatalyst is a splendid example of the green reaction with improved yields. The molecular docking analysis of compounds 5i–w were investigated with enoyl-acyl carrier protein reductase (InhA) enzyme (PDB ID: 4TZK) as anti-tubercular target molecules. The docking study implied that the synthesized compounds exhibited favorable binding modes and affinity. Further, the anti-tubercular activity was investigated against Mycobacterium tuberculosis (MTB) H37Rv strain which demonstrated that the compounds 5i, 5j, 5k, and 5l exhibited excellent activity at the 6.25 µg/ml concentrations, whereas the compounds 5m, 5n, 5o, 5s, and 5w have shown the activity at 12.50 µg/ml concentration, respectively. [ABSTRACT FROM AUTHOR]

A remarkable, efficacious, and environmental friendly one‐pot procedure affianced for the synthesis of 1,2,3‐triazoles by 1,3‐dipolar cycloaddition of aromatic azides, terminal alkynes over Cu microcrystals (CuMCs) by click chemistry as subsequent way. The predominance of this method is green synthetic pathway, transient reaction times, facile workup, exceptional yields (87% to 90%) with excellent purity, regioselective single product formation, and eco‐friendliness of the CuMCs catalyst. Docking studies manifested strong binding interactions with enzyme sterol 14‐alpha‐demethylase (PDB ID: 3KHM) with excellent C‐score values. The antifungal screening of synthesized compounds revealed promising activity. [ABSTRACT FROM AUTHOR]

Series of indole‐1,3,4‐thiadiazole compounds (IT 1–7) were synthesized and characterized by FT‐IR, 1H NMR, 13C NMR and ESI‐MS spectral data. Further, the compounds (IT 1–7) were screened for antidiabetic, antioxidant and anti‐inflammatory activities. Most of these compounds exhibited moderate to good antidiabetic, antioxidant and anti‐inflammatory activities against α‐amylase enzyme, ABTS and lipoxygenase enzyme, respectively. Among these, IT‐1 displayed the better activity compared to that of standard drugs. The mechanism of binding of IT‐1, IT‐5 and IT‐6 with a transporter protein, human serum albumin was investigated by fluorescence spectroscopic and circular dichroism studies. These compounds quenched the intrinsic fluorescence intensity of HSA and moderate binding was evident from the values of binding constants which are in the order of 105 M−1. The molecular docking studies of the compounds were performed against human pancreatic alpha‐amylase in complex with montbretin A (PDB ID: 4W93). The studied compounds interacted with amino acid residues (ASP197, GLU240 and TYR151) which were similar to that of the reference drug, acarbose. The ADME properties of designed compounds were studied using SwissADME software. All the compounds obeyed Lipinski's rule of five. All the compounds showed low or non‐toxicity towards different toxicity classes as analyzed using ProTox‐II online tool. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • A series of pyrrolyl benzamide derivatives have been designed and synthesized. • Compounds were characterized by IR, 1H NMR, 13C NMR and mass spectral analysis. • Compounds were evaluated antitubercular activity against Mycobacterium tuberculosis H 37 Rv and MDR-TB. • All the compounds exhibited good antimicrobial activities. Abstract In an effort to produce new lead antimycobacterial compounds, herein we have reported the synthesis of a sequence of new pyrrolyl benzamide derivatives. The new chemical entities were screened to target enoyl-ACP reductase enzyme, which is one of the key enzymes of M. tuberculosis that are involved in type II fatty acid biosynthetic pathway. Compound 3q exhibited H-bonding interactions with Tyr158, Thr196 and co-factor NAD+ that binds the active site of InhA. All the pyrrolyl benzamide compounds were evaluated as inhibitors of M. tuberculosis H 37 Rv as well as inhibitors of InhA. Among them, few representative compounds were tested for mammalian cell toxicity on the human lung cancer cell-line (A549) and MV cell line that presented no cytotoxicity. Five of these compounds exhibited a good activity against InhA. [ABSTRACT FROM AUTHOR]

We present a study on a new class of Schiff bases with pyrimidine linked hydrazinyl azole backbone. These compounds were synthesized using conventional and ultrasonication methods. Our design strategy incorporated three heteroaromatic azoles and various substituents on the pyrimidine scaffold to enhance antimicrobial properties. Antibacterial and antifungal screenings were conducted against specific pathogens, and molecular docking studies supported the results. The compounds exhibited significant antimicrobial activities, particularly against K. pneumoniae, surpassing the standard drug. These Schiff bases hold promise as potential antimicrobial agents. [ABSTRACT FROM AUTHOR]

In efforts to develop new antitubercular agents, we report here the synthesis of a series of novel pyrrole hydrazine derivatives. The molecules were evaluated against inhibitors of InhA, which is one of the key enzymes involved in type II fatty acid biosynthetic pathway of the mycobacterial cell wall as well as inhibitors of Mycobacterium tuberculosis H37Rv. The binding mode of compounds at the active site of enoyl-ACP reductase was explored using the surflex-docking method. The model suggests one or two H-bonding interactions between the compounds and the InhA enzyme. Some compounds exhibited good activities against InhA in addition to promising activities against M. tuberculosis. [ABSTRACT FROM AUTHOR]

In efforts to develop lead anti-TB compounds, a novel series of 19 pyrrolyl benzohydrazides were synthesized and screened to target enoyl-ACP reductase enzyme, which is one of the important enzymes involved in type II fatty acid biosynthetic pathway of M. tuberculosis . Pharmacophores were constructed using GALAHAD to generate alignment of data sets and calculated by Pareto ranking. The pharmacophore features were then filtered by Surflex-dock study using enoyl ACP reductase from M. tuberculosis . Compounds 5b and 5d showed H-bonding interactions with Tyr158, Thr196 and co-factor NAD + that fitted well within the binding pocket of InhA. All the synthesized compounds were screened for preliminary antibacterial activities against Gram-positive S. aureus and Gram-negative E. coli and M. tuberculosis H 37 Rv to evaluate their antitubercular activities. Some representative compounds were further tested for mammalian cell toxicity using human lung cancer cell-line (A549) that was found to be nontoxic. These compounds exhibited moderate inhibition activities against InhA. [ABSTRACT FROM AUTHOR]

Novel pyrrolyl hydrazones and their copper complexes have been synthesized and characterized using analytical and spectral techniques to show the tetrahedral geometry for Cu(II) complexes. Biological activities of hydrazones have been assessed to understand the role of metal ion on their biological activity and the effect of pyrrolyl hydrazones. In vitro antitubercular activity against Mycobacterium tuberculosis of the metal complexes ( 13b and 13r ) exhibited the highest antitubercular activity that are quite close to rifampicin (0.4 μg/mL), giving a MIC of 0.8 μg/mL. All other compounds showed good activity with the MIC values ranging from 1.6 to 100 μg/mL. A comparative study of inhibition values of the ligands and their complexes showed higher antimicrobial activity of the complexes than the ligands. Some compounds have a good activity against InhA and in particular, compounds 12r , 13b and 13r exhibited more than 60% binding with the enzyme even at 5 μM (exhibited good IC50 upto 2.4 μM). Most of the active molecules have a very less cytotoxicity against the human lung cancer cell-line A549. The docking and 3D-QSAR studies have been carried out to provide some insights into the mechanism of action for this class of compounds. [ABSTRACT FROM AUTHOR]

We report here the synthesis, antibacterial and antitubercular evaluation of 61 novel pyrrolyl derivatives bearing pyrazoline, isoxazole and phenyl thiourea moieties. Molecular docking was carried out on enoyl ACP reductase from Mycobacterium tuberculsosis using Surflex-Dock, which is one of the key enzymes involved in type II fatty acid biosynthetic pathway of Mycobacterium tuberculosis , an attractive target for designing novel antitubercular agents. Docking analysis of the crystal structure of ENR performed using Surflex-Dock in Sybyl-X 2.0 software indicates the occupation of substituted pyrrolyl derivatives into hydrophobic pocket of InhA enzyme. Compounds 9b and 9d exhibited the highest antitubercular activity almost close to isoniazid (0.4 μg/mL) with a MIC value of 0.8 μg/mL. All other compounds showed the good activity with a MIC value of 6.25–100 μg/mL. The compounds were further tested for mammalian cell toxicity using human lung cancer cell-line (A549) and were nontoxic. Some compounds exhibited inhibition activities against InhA. [ABSTRACT FROM AUTHOR]

A new series of pyrrolyl phenoxy derivatives bearing alkoxy linker were synthesized and evaluated for anti-tubercular activity (anti-TB) against Mycobacterium tuberculosis . Molecular modeling, pharmacophore constructed using GALAHAD to produce an effective alignment of data set and evaluated by Pareto ranking. The pharmacophore features were filtered by Surflex-dock study using enoyl ACP reductase from M. tuberculosis , which is one of the key enzymes involved in type II fatty acid biosynthesis pathway of M. tuberculosis . Compound 6a27 showed the H-bond with NAD + , whereas compound 6a26 showed H-bonds with Tyr158, Thr196, Met199 and NAD + that fitted well into the binding pocket of target InhA. The alkoxy linker bridge and acceptor groups with benzene ring were advantageous for anti-TB activity, which merit further investigation. [ABSTRACT FROM AUTHOR]

Enoyl acyl carrier protein reductase (ENR) is an essential type II fatty acid synthase (FAS-II) pathway enzyme that is an attractive target for designing novel antitubercular agents. Herein, we report sixty-eight novel pyrrolyl substituted aryloxy-1,3,4-thiadiazoles synthesized by three-step optimization processes. Three-dimensional quantitative structure–activity relationships (3D-QSAR) were established for pyrrolyl substituted aryloxy-1,3,4-thiadiazole series of InhA inhibitors using the comparative molecular field analysis (CoMFA). Docking analysis of the crystal structure of ENR performed by using Surflex-Dock in Sybyl-X 2.0 software indicates the occupation of pyrrolyl substituted aryloxy 1,3,4-thiadiazole into hydrophobic pocket of InhA enzyme. Based on docking and database alignment rules, two computational models were established to compare their statistical results. The analysis of 3D contour plots allowed us to investigate the effect of different substituent groups at different positions of the common scaffold. In vitro testing of ligands using biological assays substantiated the efficacy of ligands that were screened through in silico methods. [ABSTRACT FROM AUTHOR]

A new class of bis(azolyl) pyridine‐2,6‐dicarboxamides based derivatives were designed and synthesized by employing ultrasonication methodology. In this work, we studied the role of different heteroaromatic azole units such as oxazole, thiazole and imidazole moieties along with different donating/withdrawing substituents on the pyridine scaffold and anticipated to display good biological activities. The detailed molecular docking studies validates the antimicrobial activities of these targeted molecules. Further, to evaluate their antioxidant properties, the target compounds were exposed to three different invitro free radical scavenging assay methods. Further, using the disc diffusion method, the targeted molecules were screened for invitro antibacterial activities against the pathogenic stains. Besides, the targeted molecules were also tested against A. niger and P. chrysogenum strains to assess their antifungal activity. The screening results reveals that, the most of the compounds form the series demonstrating reasonable to decent antioxidant and antimicrobial activities against pathogenic stains in comparison with the standard drug. [ABSTRACT FROM AUTHOR]

Abstract: In order to develop a lead antimycobacterium tuberculosis compound, a series of 52, novel pyrrole hydrazine derivatives have been synthesized and screened which target the essential enoyl-ACP reductase. The binding mode of the compounds at the active site of enoyl-ACP reductase was explored using surflex-docking method. The binding model suggests one or two hydrogen bonding interactions between pyrrole hydrazones and InhA enzyme. Highly active compound 5r (MIC 0.2 μg/mL) showed hydrogen bonding interactions with Tyr158 and NAD+ in the same manner as those of ligands PT70 and triclosan. The CoMFA and CoMSIA models generated with database alignment were the best in terms of overall statistics. The predictive ability of the CoMFA and CoMSIA models was determined using a test set of 13 compounds, which gave predictive correlation coefficients (r pred 2) of 0.896 and 0.930, respectively. [Copyright &y& Elsevier]

[Display omitted] In the present study, dopamine interaction with bovine serum albumin was investigated using fluorescence, UV–vis, Raman, CV, FTIR and molecular modeling techniques. The fluorescence study of the quenching was carried out at an excitation wavelength of 296.0 nm, and the emission was measured in the range of 300–600 nm. BSA was quenched through both static and dynamic mechanisms. Thermodynamic parameters were derived to study the binding forces involved. The average binding distance between BSA and dopamine was determined using FÖrsters theory. Lifetime measurements, synchronous fluorescence and 3D spectra supported the hypotheses derived from the fluorescence data. The presence of some common co-existent drugs and the effect of essential biological metal ions were also investigated. [ABSTRACT FROM AUTHOR]

In this study, new series of N'-(2-(substitutedphenoxy)acetyl)-4-(1H-pyrrol-1-yl)benzohydrazides (3a-j) 4-(2,5-dimethyl-1H-pyrrol-1-yl)-N'-(2-(substitutedphenoxy)acetyl)benzohydrazides (5a-j) were synthesized, characterized and assessed as inhibitors of enoyl ACP reductase and DHFR. Most of the compounds exhibited dual inhibition against the enzymes enoyl ACP reductase and DHFR. Several synthesized substances also demonstrated significant antibacterial and antitubercular properties. A molecular docking analysis was conducted in order to determine the potential mechanism of action of the synthesized compounds. The results indicated that there were binding interactions seen with the active sites of dihydrofolate reductase and enoyl ACP reductase. Additionally, important structural details were identified that play a critical role in sustaining the dual inhibitory activity. These findings were useful for the development of future dual inhibitors. Therefore, this study provided strong evidence that several synthesized molecules could exert their antitubercular properties at the cellular level through multi-target inhibition. By shedding light on the mechanisms through which these compounds exert their inhibitory effects, this research opens up promising avenues for the future development of dual inhibitors with enhanced antibacterial and antitubercular properties. The study's findings underscore the importance of multi-target approaches in drug design, providing a strong foundation for the design and optimization of novel compounds that can effectively target bacterial infections at the cellular level. [ABSTRACT FROM AUTHOR]

Novel biphenyl compounds bearing triazolones have been designed and synthesized with an aim to explore the paramount set of molecules as antihypertensive agents. Our efforts have been directed towards the synthesis of Triazolyl‐biphenyl compounds containing different groups at ortho position of the biphenyl ring. In particular, cyano, tetrazole and oxadiazole substituents at the ortho position of biphenyl ring were synthesized and structures of all these previously unknown 16 molecules were confirmed by their spectral characterizations. Binding modes for these compounds were evaluated by docking in a theoretical Human angiotensin converting enzyme (ACE) in complex with Lisinopril. These novel compounds were evaluated for the in vitro ACE inhibition and the results were compared to Lisinopril. Results indicated that the tetrazole containing compounds have shown significant inhibitory activity than the other compounds which are in good agreement with the docking results. [ABSTRACT FROM AUTHOR]

In the present work, Fe3O4 nanoparticles were prepared by the co‐precipitation method and employed as effective nanocatalysts in the tandem synthesis of 3‐(4,5‐diaryl‐1H‐imidazol‐2‐yl)quinolin‐2‐amines. An effective multicomponent reaction is plighted for 2‐chloroquinoline‐3‐carbaldehydes and substituted benzils to obtain novel heterocycles 3‐(4,5‐diaryl‐1H‐imidazol‐2‐yl)quinolin‐2‐amines. These molecules are fluorescent and hence for proper understanding of optical behaviour, solvatochromic and DFT studies were carried out. Also, the optical and energy bandgaps were calculated. Molecular docking studies manifested the strong binding affinities by these compounds at the active site of the Candida albicans dihydrofolate reductase enzyme (PDB ID: 1AI9) and Novobiocin (PDB ID: 4URO) with excellent C‐score values. Antimicrobial activity screening results have shown remarkable activity against Escherichia coli with appreciable MIC values and hence noteworthy action has been demonstrated against this bacterium. The zones of inhibition for some of the target compounds are also good against gram positive Staphylococcus aureus exhibiting excellent activity. [ABSTRACT FROM AUTHOR]

A novel series of 3-aryloxyethyl-4-arylidene amino-5-mercapto-1,2,4-triazoles were prepared from 5-(α-aryloxy ethyl)-1,2,4 triazole, The structures of new compounds have been established by spectral and analytical data. The newly synthesized compounds have been tested for their antimicrobial activity. [ABSTRACT FROM AUTHOR]

• A practical method for the easy access to ureas is documented. • Good functional group tolerance. • Excellent docking scores were observed. • Extensive biological screening for both bacteria and fungi are reported. • Comprehensive adducts' characterization was performed. A series of new urea derivatives (3a-p) have been synthesized from readily available isocyanates and amines in good to high yields. All synthesized compounds were fully characterized using 1H NMR, 13C NMR, IR, and mass spectrometry. Additionally, the structure of the compound (3n) was confirmed by single-crystal X-ray diffraction. Furthermore, all compounds were evaluated for antimicrobial activity against five bacteria and two fungi. Last but not the least, molecular docking studies with Candida albicans dihydropteroate synthetase were performed and the results are presented herein. [ABSTRACT FROM AUTHOR]

Using 2-(9H-fluoren-9-ylidene)hydrazinyl)thiazol-4(5H)-one and substituted benzaldehydes, a new library of fluorenone–thiazolidine-4-one scaffolds (5a–u) were synthesized and characterized using FT-IR, 1H NMR, 13C NMR and mass spectral data. Single crystals of compound 5s were developed and crystallographic data were collected. Hirshfeld surface evaluation was used to investigate the intermolecular interactions that exist within the crystals. The synthesized compounds were screened for in vitro antioxidant and anti-diabetic properties by DPPH scavenging activity and α-glucosidase inhibition, respectively. Compounds 5a–l exhibited promising DPPH scavenging activity. Compound 5l showed an IC50 value of 27.70 ± 0.8 μM, which is 4.25-fold greater as compared to that of the standard, gallic acid (an IC50 value of 117.92 ± 2.8 μM). Compound 5g exhibited good α-glucosidase inhibition with an IC50 value of 114.58 ± 1.6 μM, which is less than that of the standard inhibitor, acarbose, with an IC50 value of 115.49 ± 2.2 μM. The mechanism of binding of compound 5g with human serum albumin (HSA) and calf thymus DNA (Ct-DNA) was studied by fluorescence spectroscopy. Furthermore, the ADME properties of the designed compounds were studied using the SwissADME online tool. The molecular docking studies of the compounds were performed against acid-α-glucosidase, in complex with 1-deoxynojirimycin (PDB ID: 5NN5). [ABSTRACT FROM AUTHOR]

A proficient copper(I) catalyzed three-component synthetic protocol has been established for the synthesis of medicinally essential substituted imidazo[1,2-a]pyridines by means of C–H bond amination followed by acetylene incorporation under microwave irradiation. The biological results and computational analysis suggested that the compounds had a greater affinity for the COX-2 enzyme than for the COX-1 enzyme. The investigation of docked (PDB ID: 5IKR ; A-chain) postures of the compounds exemplified that they embrace similar configurations to the exceedingly selective COX-2 inhibitor. The compounds 8e, 8h, 8l, 8n, 8p, 8r, 8t, 8v and 8x originated as the most efficient and selective COX-2 inhibitors with IC50 values of 18.94, 0.02, 3.28, 0.067, 0.05, 19.42, 3.66, 0.19 and 24.59 μg mL−1 respectively in contrast to mefenamic acid (25.74 μg mL−1). The selectivity index was obtained for all the significantly active molecules. Excitingly, the molecules that were effective as COX-2 inhibitors were active as antioxidant agents as well. [ABSTRACT FROM AUTHOR]

The article focuses on the research titled "Pyrrole: Chemical Synthesis, Microwave Assisted Synthesis, Reactions and Applications: A Review" by researchers S.D. Joshi, U.A. More, V.H. Kulkarni and others published in the journal "Current Organic Chemistry" in 2013.

Bacterial infections are increasingly difficult to combat as bacteria evolve resistance to antibiotic drugs and have severely compromised the arsenal of antibiotic drugs. On the other hand matrix metalloproteinases (MMPs) play a fundamental role in inflammation and extracellular matrix degradation in physiological and pathological conditions. In search of potent antibiotic, taking coumarin and dihydropyrimidinone as lead compound, a green, eco-friendly and efficient protocol has been developed and synthesized the dihydropyrimidin-2(1 H )-one/thione derivatives of coumarin 3/4 from substituted 4-formylcoumarins 2 and ethylacetoacetate using urea/thiourea in the presence of catalytic amount of ceric ammonium nitrate is reported. All the synthesized compounds were evaluated for their antibacterial activity against four bacterial strains by broth dilution method. The tested compounds have exhibited promising in vitro potency with low MIC values against the drug susceptive S. aureus strain with low MIC values ranging from 0.2 to 6.25 μg/mL. The in vivo anti-inflammatory potency of 3a–e and 4a–e by gelatin zymography is comparable to that of tetracycline. Molecular docking study performed for all the synthesized compounds with S. aureus DNA gyrase and results obtained were quite promising. [ABSTRACT FROM AUTHOR]

2-Propargylthiobenzimidazole 1 , 4-bromomethyl coumarins/1-aza-coumarins 2 / 3 and sodium azide have been reacted in one pot under Click chemistry conditions to give exclusively 1,4-disubstituted triazoles 5a – n . Anti-tubercular assays against M. tuberculosis (H 37 Rv) coupled with in silico molecular docking studies indicated that dimethyl substituents 5c and 5d showed promising activity with higher C-score values. [ABSTRACT FROM AUTHOR]

The 2-substituted benzoxazole derivatives are known to exhibit a wide spectrum of biological potential. Two series of novel benzoxazole derivatives containing 2-phenyl and 2-N-phenyl groups were synthesized, by following the green chemistry approach. All the newly synthesized derivatives were screened against gram-positive bacteria (Streptococcus pyogenes, Staphylococcus aureus), gramnegative bacteria (Pseudomonas aeruginosa, Escherichia coli) and the fungus (Aspergillus clavatus and Candida albicans). Most of these compounds have demonstrated potent antibacterial activities, especially against E. coli at 25 μg/mL, along with moderate antifungal activity. Among these, two compounds, 21 and 18, showed interesting antibacterial profile. Molecular docking studies suggested that the antibacterial activity can be linked to the inhibition of DNA gyrase. Overall, the study proposes that these biologically potent compounds can be considered for developing the next generation antimicrobial agents. [ABSTRACT FROM AUTHOR]

A series of new Coumarin hydrazone oxime scaffolds were synthesised as potential anti‐TB agents. The structures of the scaffolds were confirmed by spectroscopic and analytical techniques. X‐ray crystallography confirmed the structure of compound 6‐methyl‐4‐((((Z)‐((E)‐3‐(2‐phenylhydrazono)butan‐2‐ylidene)amino)oxy)methyl)‐2H‐chromen‐2‐one (5a). The coumarin hydrazone oxime scaffolds were tested in‐vitro against the Mycobacterium tuberculosis H37Rv strain, and Vero cells were used to assess cytotoxicity. Compound 5b was obtained as the hit candidate, exhibiting MIC 0.78 μg/mL, showing more potent anti‐TB activity than Rifamycin and comparable activity to Isoniazid. There was minimal cytotoxicity observed against Vero cells for the most active compounds, indicating a good safety‐profile.In addition, the most diligent compound 5b demonstrated substantial binding interactions at the PDB:4DQU enzyme's active site and also displayed greater C‐score value than that of 4DQU ligand which validates the observed results. [ABSTRACT FROM AUTHOR]

1,2,4-Triazoles and 1,3,4-oxadiazoles independently are very important pharmacophores. In view of this, a new class of 1,2,4-triazole clubbed with 1,3,4-oxadiazole motifs have been prepared and characterized by IR, ¹H NMR, 13C NMR and mass spectral analysis. Molecular docking of all the title compounds into S. aureus tyrosyl-tRNA synthetase (PDB: 1JIJ) and lanosterol 14α-demethylase complex with standard inhibitor Fluconazole (PDB: 3KHM) is performed which snugly fitted into the active site thus explaining their excellent inhibitory activity exhibiting their possible antibacterial and antifungal activity, respectively. Drug-likeliness, Drug score values and toxicity prediction analyses of all the title compounds have shown favourable values and these molecules belong to Class 4 and Class 5 categories which make them useful scaffolds. Interestingly, the compounds 7h, 7i, 7k, 7u and 7v have exhibited majestic antibacterial activity. Also, these compounds have shown antifungal activity against all pathogenic fungal strains with lower MIC value ranging from 0.50 - 4.00 µg/mL. [ABSTRACT FROM AUTHOR]

An influential method for the synthesis of imidazo[2,1‐b]thiazoles via copper (I) catalysis was advanced through a multicomponent coupling of pharmacological scaffolds involving 2‐aminothiazolyl‐coumarin, benzaldehyde, and phenyl acetylene, a concealed variation. The protocol allows the establishment of highly efficient and user‐friendly catalytic system for the A3 cascade coupling; also, an environmentally benign, economical, and readily obtainable CuSO4/sodium ascorbate is portrayed. A sequence of 15 novel imidazo[2,1‐b]thiazoles (7j–x) were synthesized and evaluated for their in vitro antimicrobial activity, in silico studies, and oral toxicity studies. The in vitro antifungal and antibacterial screening of synthesized compounds manifested favorable activity and disclosed that all these previously unknown compounds showed significant activity. Amid them, compound 7u portrayed the most effective inhibitory activity. [ABSTRACT FROM AUTHOR]

Enoyl Acyl Carrier Protein (ACP) Reductase, a key enzyme, which catalyzes the last reductive step of fatty acid biosynthesis and it, is one of the key enzymes for the development of antitubercular agents. In this pursuit, molecular docking and 3D-QSAR studies (CoMFA and CoMSIA) have been performed on a series of pyrimidine derivatives (29 compounds) to understand the binding sites, interactions to improve over the existing leads in terms of improved biological and physico-chemical properties. Molecular docking was performed on a protein InhA (T2A mutant) (PDB ID: 5OIR) using the Surflex-Dock suite available in SYBYL-X 2.1.1 (Tripose Inc., USA). In addition, 3D-QSAR studies have been performed to validate the models using the data set, which was segregated into training and test set by using the Diversity and Dissimilarity method. Structural features required for the prediction of better inhibitory potency was generated in the form of contour maps from the CoMFA and CoMSIA models (Steric, Electrostatic, Hydrophobicity, H-bond donor and acceptor maps) and predicted values for r2 = 0.966, q2 = 0.22 for the CoMFA model and r2 = 0.925, q2 = 0.576 for the CoMSIA model. From this study, it is observed that interaction with amino acid residues TYR158, MET199, MET161, GLY96, and PHE97 are important for the activity that helped to predict SARs by providing important structural features. Both the models were good in understanding the specific activity of some of the compounds that will facilitate to develop new types of Enoyl ACP reductase inhibitors. [ABSTRACT FROM AUTHOR]

Biomolecular interaction of hydralazine with human serum albumin (HSA) was studied by fluorescence, ultravoilet, three-dimensional, synchronous, Fourier transform infrared, lifetime fluorescence, resonance Rayleigh scattering, circular dichroism, and molecular docking techniques. The intrinsic fluorescence of HSA was quenched by a static quenching mechanism. The effect of β-cyclodextrin on binding was studied. Binding constants and number of binding sites were evaluated using the Stern-Volmer equation. Thermodynamic parameters (ΔH°, ΔG°, and ΔS°) indicate the involvement of hydrogen bonding with weak van der Waals forces in the interaction. The average binding distance (r) between the HSA and hydralazine was calculated by Fourier resonance energy transfer theory. Molecular docking study confirms the drug binding sites and interaction of hydralazine with amino acid residues. [ABSTRACT FROM AUTHOR]

A green, commodious, immensely versatile synthetic route for agro waste extract WELPSA catalyzed cyclocondensation of biologically active triazolothiadiazine‐coumarin hybrid derivatives has been studied. A proficient synthesis offused heterocycles 9 i–wvia dehydrative condensation with cyclization of4‐((4‐amino‐5‐mercapto‐4H‐1,2,4‐triazol‐3‐yl)methyl)‐2‐aryl‐2,4‐dihydro‐3H‐1,2,4‐triazol‐3‐one (5 a‐‐c) and substituted bromoacyl coumarins (8 d‐‐h)has been incorporated in presence of different catalysts including WELPSA, a green catalyst. The in silico docking studies of these previously unknown compounds revealed favorable C score and Chemscore values and the in vitro antifungal assay against three fungal strains showed excellent to good activity. [ABSTRACT FROM AUTHOR]

A series of novel acridine-thiazole bridged coumarin derivatives 3a–3i were designed, synthesized and subjected for their in-vitro antiproliferative activity on human breast cancer (MDA-MB-231), lung cancer (A-549) and colon cancer (HT29) cell lines. In case of human breast (MDA-MB-231) cell line, among the nine screened compounds, 3d, 3c, 3g, and 3a exhibited moderate to good antiproliferative activity with IC50 values in the range 14.06–8.03 µM concentration. The compound 3d exhibited higher activity with IC50 value 8.03 µg/mL, compared to 3c with IC50 value of 12.03 µg/mL. Whereas, compounds 3g, 3b, 3h, 3a, and 3i also exhibited significant cytotoxicity with IC50 values in the range 05.18–18.17 µM concentration. Further, the compound 3g exhibited distinct activity with IC50 value 05.18 µg/mL, followed by compound 3b with IC50value of 09.09 µg/mL for A-549 cancer cell line. However, for HT29 cell line all of the compounds showed significantly lesser activity when compared with standard drug Cisplatin. In addition, the synthesized compounds were screened for their anti-TB activity and its cytotoxicity, the compound 3g exhibited excellent antitubercular activity with MIC of 0.78 µg/mL, while the compound 3b exhibiting MIC of 1.56 µg/mL with the highest safety percentage survival of 72% and 78%. [ABSTRACT FROM AUTHOR]

• Library of 2,5 and 1,5-Regioisomers of 5-substituted tetrazoles were designed and synthesized. • The compounds were screened for in vitro anticancer and antifungal activity. • All the compounds exhibit good safety profile in HCT-116 colon cancer cell lines. • Amongst all compounds 6h, 6g, 6i have the highest zone of inhibition and 6g, 5f have excellent activity with very low IC 50 values were found as good hits. • Computational toxicity and in silico studies was done for them. A novel series of compounds was synthesized using 3-arylsydnone 1a-b. Initially, 3-arylsydnone was converted into 1-aryl-1 H- pyrazole-3-carbonitriles 2a-b via [3+2] cycloaddition with acrylonitrile by ring transformation which once again underwent [2+3] cycloaddition with sodium azide to afford 5-(1-aryl-1 H -pyrazol-3-yl)-1 H -tetrazoles 3a-b.These were subjected to N-alkylation with 4-bromomethyl coumarins 4c-e to afford regioisomers viz., 2,5- and 1,5-disubstituted tetrazole derivatives 5f-k and 6f-k. Single crystal X-ray analysis of compound 6f was carried out. All the synthesized compounds were characterized using various techniques including 1H NMR, 13C NMR, FT-IR, elemental analysis, and mass spectroscopy.These previously unknown compounds were screened for their anticancer activity against HCT-116 colon cancer and non-cancerous L929 cell line at a single high dose (10−5 M) concentration assay. Among the tested compounds, 6g and 5f have exhibited excellent activity with very low IC 50 value i. e.,27.85 µg/mLand 37.86 µg/mL respectively, comparable with standard Cisplatin. In the non-cancerous L929 cell line, the tested compound 6f was proven to be less toxic, and all the tested compounds exhibited toxicity at higher concentrations comparable with standard Cisplatin. Further, the in vitro antifungal activity against Candida albicans for these compounds 5f-k and 6f-k revealed potential to moderate activities compared to the standard. Moreover, docking analysis was performed to know the exact binding mode of the newly synthesized compounds with N- myristoyltransferase (PDB ID: 1IYL) from Candida albicans which was selected as the antifungal targets. The drug-likeness of the compound was assessed using Molinspiration, while the toxicity profile was evaluated using Protox. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: Two series of 4-aryloxymethyl coumarins derived from the reaction of 4-bromomethyl coumarins with ethyl gallate and ethyl ester of N-Benzoyl tyrosine have been synthesized. Gallate ethers 3a–3g and tyrosine derivatives 4e–4j were most effective against Entercoccus faecalis. They were also found to be effective against Aspergillus niger and Candida albicans. Comparative docking studies with novobiocin have indicated better binding ability and higher ‘C’ score values than novobiocin. [Copyright &y& Elsevier]

[Display omitted] • 1,3,4-oxadiazole-thiazolidine-2,4-dione hybrid compounds (TOT-1 to 15) were synthesized, characterized and screened for various biological activities. • Single-crystal X-ray diffraction data was collected for the intermediate compound, TOT and its structure was proposed. • The compounds, TOT 12–15 exhibited significant anti-cancer activity. • Molecular docking studies were carried out. Two synthetic methods were proposed for the preparation of a new series of thiophene-1,3,4-oxadiazole-thiazolidine-2,4-dione hybrids (TOT-1 to 15) and their structures were elucidated based on spectral data. Studies on cytotoxicity, ROS, cellular uptake and interactions of TOT-14 with calf thymus DNA were carried out. Anticancer activity of compounds, TOT-1 to 15 on breast cancer (MCF-7) cell lines was investigated. The IC 50 values for the standard, epirubicin hydrochloride and TOT-12, 13, 14 and 15 were found to be 6.78, 5.52, 6.53, 4.83 and 5.57 µg/mL, respectively. Notably, TOT-14 exhibited a remarkable antiproliferative activity with a strikingly selective inhibitory effect compared to standard. This specific selectivity could be attributed to the synergistic effect of increased cellular uptake and generation of higher ROS in cancer cells after irradiation. The binding constant of 4.25 x 103 M−1 indicated the moderate interaction between TOT-14 and ct-DNA. The docking score of TOT derivatives was substantially identical to the docking score of epirubicin hydrochloride. The designed molecules complied with the requirements for drug-likeness and ADME. [ABSTRACT FROM AUTHOR]

Since 2019, the infection of SARS‐CoV‐2 has been spreading worldwide and caused potentially lethal health problems. In view of this, the present study explores the most commodious and environmentally benign synthetic protocol for the synthesis of tetrahydrobenzo[b]pyran and pyrano[2,3‐d]pyrimidinones as SARS‐CoV‐2 inhibitors via three‐component cycloaddition of aromatic aldehyde, malononitrile, and dimedone/barbituric acid in water. Lemon peel from juice factory waste, namely, lemon (Citrus limon), sweet lemon (C. limetta), and Kaffir lime or Citron (C. hystrix), effectually utilized to obtain WELPSA, WESLPSA, and WEKLPSA, respectively, for the synthesis of title compounds. The catalyst was characterized by scanning electron microscope (SEM) and energy‐dispersive x‐ray spectroscopy (EDX). The concentration of sodium, potassium, calcium, and magnesium in the catalyst (WELPSA) was determined using atomic absorption spectrometry (AAS). The current approach manifests numerous notable advantages that include ease of preparation, handling and benignity of the catalyst, low cost, green reaction conditions, facile workup, excellent yields (93%–97%) with extreme purity, and recyclability of the catalyst. Compounds were docked on the crystal structure of SARS‐CoV‐2 (PDB: 6M3M). The consensus score obtained in the range 2.47–4.63 suggests that docking study was optimistic indicating the summary of all forces of interaction between ligands and the protein. [ABSTRACT FROM AUTHOR]

4-((4-((Benzo[d]oxazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)methyl)-2H-chromen-2-ones 7k–z were synthesized by conventional as well as microwave irradiation method in order to obtain antimicrobial agents. The present green synthetic protocol explores facile work up procedure with excellent yields (82–92%) and purity. Docking studies exhibited strong binding interactions with enzyme N-myristoyl transferase (PDB ID: 4CAW) with excellent C-score values. Compounds 7k–z were screened for their in vitro antimicrobial activities. The compounds 7w and 7 y exhibited excellent antimicrobial results for all the tested microorganisms at MICs ranging from 3.12 to 6.25 µg/ml in comparison with the marketed drugs. [ABSTRACT FROM AUTHOR]

In this paper, the synthesis of novel pyrazoles and their in vitro anti-inflammatory and in-vitro antifungal assay have been reported. These compounds were docked into the inducible nitric oxide synthase (iNOS) oxygenase dimer. The compounds 3c, 7a, 7c, 8a, 8c have exhibited the C-score values more than the standard drug aminoguanidine (5.35). Upon the favorable docking results, the anti-inflammatory potential of the title compounds was determined by analyzing the reduction in the NO production by activated macrophages using in-vitro assays. The compounds 4c, 5c, 6a, 6c, 7a, 8a, 8c exhibited the potential anti-inflammatory activity at 1.00 µg/mL. Further, the docking study of the title compounds 3b, 3c, 4a, 5a, 5c with Aspergillus fumigatus N-myristoyl transferase (NMT) showed appreciable C-score values as against that of fluconazole (5.56). This observation was further substantiated by in-vitro antifungal activity in which the compounds 3b–c, 4a–c, 5a–c, 6a–c, 7a–b, 9a–c have excellent inhibition against A. fumigatus. [ABSTRACT FROM AUTHOR]

• A series of new coumarino-azetidinones (3a-l) were designed and synthesized. • All the compounds were screened for antitubercular and antimicrobial activity. • Compounds 3e and 3k emerged out as promising antituberculars and antimicrobials. • Compounds 3e and 3k were exhibited comparatively less toxicity. • Excellent molecular docking scores were observed. In the present work, a series of new coumarino-azetidinones (3a-l) were designed, synthesized and evaluated for biological activities. The newly synthesized compounds (3a-l) were fully characterized by several spectroscopic techniques and elemental analyses. The synthesized compounds (3a-l) were screened for their preliminary in-vitro antitubercular and antimicrobial activities. Almost all the coumarino-azetidinones showed promising activity against Mycobacterium tuberculosis (M. tuberculosis) H 37 Rv strain. Conversely, some of the coumarino-azetidinones displayed interesting antimicrobial activities. Moreover, most active compounds were tested for cytotoxicity studies and exhibited low-level cytotoxicity towards Vero cells. Last but not the least, molecular docking results showed excellent interactions with M. tuberculosis InhA-D148G mutant (PDB. 4TZK) and Escherichia coli (E. coli) (PDB. 4JX8). The results of biological evaluation suggest that the coumarino-azetidinones are promising lead compounds for the subsequent investigation in search of new antitubercular and antimicrobial agents. Image, graphical abstract In the present study, a series of new coumarino-azetidinones were synthesized, characterized and evaluated for their preliminary antitubercular, antimicrobial and cytotoxicity activity. [ABSTRACT FROM AUTHOR]

In the present study, we reported the synthesis of benzimidazole‐containing tricyclic systems and evaluated their antimicrobial efficacy against some Gram‐positive, Gram‐negative strains, and their anti‐inflammatory activity as well as a hemolytic assay in terms of percentage. The antimicrobial study of the synthesized compounds revealed that most of them showed significant activity, and compound 5b displayed excellent antimicrobial efficacy among all. Results showed that the hydroxyl group at the fourth position on the aromatic ring has a substantial role in the biological activity. Synthesized compounds showed promising minimum inhibitory concentration (μg/mL) values in the range of 1.2–12.8 μg/mL against the tested strains. The in vitro anti‐inflammatory activity of these compounds was evaluated by denaturation of bovine serum albumin method and showed the inhibition in the range of IC50 value 31.16–94.63 μg/mL. Among all the tested compounds, compound 5b has a significant IC50 value. The percentage of hemolysis of the target compounds ranged from 1.14 to 52.8 at a concentration of 100 μg/mL. Molecular docking study revealed the good binding interactions against Escherichia coli, and it is best suited with in vitro studies. Pharmacokinetic studies showed the safe profiles for the title compounds. [ABSTRACT FROM AUTHOR]

The green chemistry approach provides for the synthesis of coumarin-1,4-dihydropyridine scaffolds 6a-o via sequential multicomponent reaction using catalytic amount of triethylamine (TEA). These new coumarin scaffolds have been successfully explored for the effective inflammatory as well as microbial infection inhibitors. The antimicrobial activity results of the title compounds have shown potent activity against both gram positive and gram negative bacterial, and fungal stains. Additionally, anti-inflammatory activity of all the compounds has been found to be quite promising in comparison with standard Diclofenac sodium. Furthermore, the in silico docking study has been performed for all the compounds with S. aureus DNA gyrase and cyclooxygenase-2 (PDB ID 4PH9). The computational results are in good agreement with the in vitro antibacterial and anti-inflammatory experimental results. [ABSTRACT FROM AUTHOR]

The six-membered ring heterocycle 1,3,5-triazine and its derivatives have attracted considerable attention as they have proven to be excellent bioactive herbicides, cancer agents, etc. A series of 1,3,5-triazine derivatives (3a-o) were synthesized by a single step reaction and characterized by 1H NMR, 13C NMR, and mass spectrometry analysis. Antimicrobial screening of title compounds (3a-o) was examined against five bacterial and two fungal strains. In vitro study revealed that the freshly synthesized 6-(thiazol-4-yl)-1,3,5-triazine-2,4-diamine (3o) showed good antibacterial growth inhibition against E. coli , K. pneumoniae , and A. baumannii bacterial strains, and even the fungi C. neoformans. Molecular docking studies were performed on the X-ray crystal structure of E. coli 24 kDa domain in complex with clorobiocin (PDB code: 1KZN; resolution 2.30 Å) using Surflex-Dock program of Sybyl-X software. The results obtained are very encouraging. Image 1 • A simple method for the direct access to 1,3,5-triazines is documented. • Good functional group tolerance, including one fluorinated compound. • Excellent molecular docking scores were observed. • Broad biological screening for both bacteria and fungi are reported. • Compound (3o) showed good antimicrobial growth inhibition. [ABSTRACT FROM AUTHOR]

• A simple method for the direct access to piperazines is documented. • Good functional group tolerance, including fluorinated compounds. • Excellent docking scores were observed. • Extensive biological screening for both bacteria and fungi are reported. • Comprehensive adducts′ characterization was performed. Herein, we describe the successful design and synthesis of seventeen new 1,4-diazinanes, compounds commonly known as piperazines. This group of piperazine derivatives (3a-q) were fully characterized by 1H NMR, 13C NMR, FT-IR, and LCMS spectral techniques. The molecular structure of piperazine derivative (3h) was further established by single crystal X-ray diffraction analysis. All reported compounds were evaluated for their antibacterial and antifungal potential against five bacterial (Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa) and two fungal strains (Candida albicans and Cryptococcus neoformans). The complete bacterial screening results are provided. As documented, piperazine derivative 3e performed the best against these bacteria. Additionally, data obtained during molecular docking studies are very encouraging with respect to potential utilization of these compounds to help overcome microbe resistance to pharmaceutical drugs, as explicitly noted in this manuscript. [ABSTRACT FROM AUTHOR]

• Cyclic ureido based mono/ bis -coumarin 'click triazoles' have been synthesized. • Newly synthesized triazoles inhibited Mycobacterium tuberculosis H37Rv. • Benzimidazolono- bis -coumarinyl triazoles exhibited lower MIC values. • Theophylline/uracil-based mono/ bis -coumarin triazoles exhibited higher MIC values. • Cytotoxicity studies exhibited IC 50 values 10 times higher than Mtb MIC values. Nucleoside bases like uracil, pharmacophoric triazoles and benzimidazolones have been used during the present study to design molecular matrices for antitubercular activity, employing Click Chemistry. Click triazoles 4 / 7 / 10 have been obtained by the reaction of 4-(Azidomethyl)-2 H -chromen-2-ones/quinolin-2(1 H)-ones 3 and propargyl ethers 2/6/9 derived from theophylline/6-methyl uracil/2-benzimidazolone respectively. In addition to spectral data structures have been confirmed by single crystal X-ray diffraction studies in case of uracil bis alkyne (6) and theophylline mono triazole (4c). Theophylline linked mono triazoles, 4 (a-d) and 6-methyl uracil linked bis triazoles, 7 (a-e) have been found to inhibit Mycobacterium tuberculosis H37Rv with MIC values in the range 55.62–115.62 μM. Benzimidazolone bis triazoles, 10 (a-n) showed better activity with MIC in the range 2.33–18.34 μM. Molecular modeling studies using Surflex-Dock algorithm supported our results. [ABSTRACT FROM AUTHOR]

In this study, we report the ring transformation of 3‐arylsydnone into 1‐aryl‐1H‐pyrazole‐3‐carbonitriles via [3 + 2] cycloaddition with acrylonitrile. 1‐Aryl‐1H‐pyrazole‐3‐carbonitrile underwent [2 + 3] cycloaddition with sodium azide to afford 5‐(1‐aryl‐1H‐pyrazol‐3‐yl)‐1H‐tetrazoles which were further subjected to N‐alkylation with aryl/heteroaryl alkyl halides to afford 1,5‐ and 2,5‐disubstituted tetrazoles. Furthermore, the title compounds were screened for in vivo antihyperglycemic activity using albino Wistar rats of either sex. Compounds 4a, 6b, 7a, 7b, 8b, and 9b showed maximum fall in the blood glucose levels in streptozotocin‐induced diabetic rats after 5–7 days of administration. In support of antidiabetic activity, we also performed the experimental in vivo studies, namely, effect of compounds on enzymes (serum glutamic oxaloacetic transaminase, serum glutamic‐pyruvic transaminase, creatinine, urea, and total protein), antihyperlipidemic, and histopathology. Moreover, the molecular docking study has been performed for potent molecules among the series with glycogen phosphorylase as target enzyme, and this study corroborated the experimental in vivo results. [ABSTRACT FROM AUTHOR]

One-pot multi-component synthesis of tri and tetra-substituted coumarin-imidazole conjugates have been achieved in good to excellent yield under conventional and microwave methods in optimized catalyst condition. Further, they have been evaluated for antimicrobial activity against Gram positive Bacillus flexus and Gram negative Pseudomonas Spp. bacterial strains and two strains of fungi Scopulariopsis spp. and Aspergillus tereus organisms. The results of microbial activity are promising against tested organisms. The molecular docking study has been performed for all the compounds and docking scores are excellent. Synthesized compounds have been characterized by IR, NMR, mass and a few of them by single crystal X-ray analysis. [ABSTRACT FROM AUTHOR]

3‐Arylsydnones are reported to possess striking pharmaceutical potency. α‐Aminoketone, a biologically active structural unit, is built at the fourth (electrophilic) position of sydnone and further derivatized with secondary amine and tetrazoles. The α‐aminoketone derivatives of sydnones coupled with secondary amines 4a–n were docked on enoyl acyl carrier protein (ACP) reductase from Mycobacterium tuberculosis, which revealed that compounds 4b, 4f, and 4i showed efficient C score values with different binding modes and hydrogen bonding. Further, these compounds were screened for antimycobacterial activity; among them, compound 4f displayed sensitivity at 6.25 μg/mL compared with the standard drug (Streptomycin) against M. tuberculosis (H37RV strain). In addition to this, α‐aminoketone derivatives of sydnones coupled with tetrazoles 8a–h were evaluated for antifungal activity. In the antifungal activity, compound 8b has exhibited potent activity at 6.25 μg/mL against Candida albicans and compound 8g at 0.4 μg/mL against Aspergillus fumigatus. The antifungal activities are comparatively better than standard antifungal agent Fluconazole at these drug concentrations. Alongside characterization of the final compounds by Fourier transform infrared, mass, 1H NMR, and 13C NMR spectral analyses, compounds 8b and 8g were confirmed by X‐ray crystallographic studies. [ABSTRACT FROM AUTHOR]