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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]

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]

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]

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]

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.

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]

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]

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]

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]

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]

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]

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]

Hit, Lead & Candidate Discovery A variety of novel 2‐(methyl/phenyl)‐3‐(4‐(5‐substituted‐1,3,4‐oxadiazol‐2‐yl)phenyl) quinazolin‐4(3H)‐ones have been synthesized by treating 3‐(4‐(5‐mercapto‐1,3,4‐oxadiazol‐2‐yl)phenyl)‐2‐(methyl/phenyl)‐quinazolin‐4(3H)‐one with a variety of secondary amines. Graph theoretical analysis was used in identification of drug target that is, NMDAR (N‐methyl‐d‐aspartate receptors). The observed reports of in silico modeling and ligand based toxicity, metabolism prediction studies were encouraging us to synthesize of title compounds and evaluate their antiepileptic effects. The title compounds were tested for its antiepileptic potency by MES and scPTZ model. Rotorod test is used to assess its neurotoxicity. In the preliminary test it was found that in MES test, analogs 6d, 6e, 6f, and 6l were potent; whereas in scPTZ test analogs 6d, 6e, 6f, and 6k displayed potent antiepileptic activity. Additionally these five derivatives were tested in rats orally at a dose of 30 mg/kg and found that compounds 2‐methyl‐3‐(4‐(5‐morpholino‐1,3,4‐oxadiazol‐2‐yl)phenyl)quinazolin‐4(3H)‐one 6e and 2‐methyl‐3‐(4‐(5‐(piperidin‐1‐yl)‐1,3,4‐oxadiazol‐2‐yl)phenyl)quinazolin‐4(3H)‐one 6f exhibited superior activity than reference Phenytoin. In MES test, these derivatives 6e and 6f showed activity at 30 mg/kg i.p. dose after 0.5 hr and 4.0 hr. In scPTZ test these derivatives 6e and 6f showed activity at 100 and 300 mg/kg i.p. dose after 0.5 hr and 4.0 hr, respectively. [ABSTRACT FROM AUTHOR]

The reaction of a multi‐substituted pyrazole 1 with aryl or heteroaryl aldehydes and active methylene compounds afford unexpected pyrazolo[1,5‐a]pyridine derivatives 4(a‐k). Mechanism for this unexpected reaction involving reactivity of the active methylene moiety with a neighboring endocyclic NH group is proposed and structure has been established by the NMR and single crystal X‐ray diffraction studies. Moreover, all the newly synthesized compounds were tested for their anticancer activity against sixty human cell lines at NCI. Among all the compounds, three scaffolds 4d, 4 h and 4k showed enhancement in anticancer activity in comparison with remaining synthesized compounds. Interestingly compound 4k was found to highly active even at a five dose concentration. The IC50 values were determined against two cell lines MCF‐7 and HepG2, the results obtained have shown promising effects against cancer cell lines. Further, the molecular docking studies revealed that substituted pyrazolo[1,5‐a]pyridine derivatives are good candidates in the medicinal field. Multi‐substituted pyrazole (1) with aryl or heteroaryl aldehydes and active methylene compounds afford unexpected pyrazolo[1,5‐a]pyridine derivatives 4(a–k). Moreover, all the newly synthesized compounds were tested for their anticancer activityagainst sixty human cell lines at NCI. Threes scaffolds (4 d), (4 h) and (4 k) showed enhancement in anticancer activity in comparison with remaining synthesized compounds. Further, the molecular docking studies revealed that substituted pyrazolo[1,5‐a]pyridinederivativesare good candidates in the medicinal field. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is still a demanding worldwide health problem and mycobacterium tuberculosis (MTB) remains one of the most toxic human pathogens. In pursuit of searching new antitubercular and antimicrobial agents, substituted coumarin and phenyl‐1,2,4‐triazolidine‐3‐thiones 4a‐i and 5a‐e have been synthesized and evaluated for their antitubercular and antimicrobial activities. Most of the Substituted coumarin and phenyl‐1,2,4‐triazolidine‐3‐thiones showed promising activity against Mycobacterium tuberculosis (H37Rv). The title compounds have exhibited excellent in vitro antibacterial activity against the S.aureus, Bacillus sps and E.coli with the values of low MIC ranging from of 0.4 to 1.6 μg/mL. In vitro antifungal activity shown that the compounds 4a‐i and 5a‐e are excellent antifungal agents against Candida albicans, Aspergillus flavus, Aspergillus niger and Aspergillus fumigate fungal stains with the values of low minimum inhibitory concentrations (MIC) ranging from 0.4 to 6.25 μg/mL. Molecular docking study was performed for all the synthesized compounds with E.coli as antibacterial and Mycobacterium tuberculosis DprE1 as antituberculosis. In pursuit of searching new antitubercular and antimicrobial agents, coumarin and phenyl‐1,2,4‐triazolidine‐3‐thiones 4a‐i and 5a‐e have been synthesized and evaluated for their antitubercular and antimicrobial activities. Most of the coumarin and phenyl‐1,2,4‐triazolidine‐3‐thiones showed promising activity against Mycobacterium tuberculosis (H37Rv). The compounds have exhibited excellent in vitro antibacterial activity against the S.aureus, Bacillus sps and E.coli. Antifungal activity shown that the compounds 4a‐i and 5a‐e are excellent antifungal agents against fungal strains. Molecular docking study was performed for all the compounds. [ABSTRACT FROM AUTHOR]

Our recent research interest regarding synthesis of bioactive furanocoumarin derivatives, we have developed pyridinium yield assisted synthesis of 2,3‐dihydrofuran coumarin derivatives via, multicomponent one step reaction with excellent yield. All compounds 4(a–p) and 6(a–b) were screened for their in vitro antimicrobial, Anti‐inflammatory and cytotoxicity activity. The activity results demonstrated that, synthesized compounds are selective against both Gram positive bacterial strains B.subtilis, S.aureus and inactive against Gram negative bacterial strains E.coli, P.aeruginosa. Similarly, compounds are highly potent against both fungal strains C.albicans and C.tropicalis over standard drugs Fuconazole. The anti‐inflammatory activity was examined using egg albumin protein denaturation and Human red blood cell membrane stabilization methods; in both methods anti‐inflammatory results are highly promising. Compounds 4 a, 4 b, 4 d and 4 o exhibited potential cytotoxic activity against lung cancer cell lines with IC50 value ranging from 0.29 to 0.35 μM. Identifying the active antimicrobial and anti‐inflammatory agent is as essential factor for the successful development of lead molecules in drug designing. Molecular docking study was performed for all the compounds and docking result reveals that compounds are possessing drug like property. Furanocoumarin derivatives are selectively active against Gram positive bacterial strains and are found to be highly potent antifungal agent. These compounds also showed promising activity against anti‐inflammatory and cytotoxic, based on these result, compounds are considered to be lead molecules in drug designing. Molecular docking study was performed for all the compounds and docking result reveals that, these compounds are possessing drug like property. [ABSTRACT FROM AUTHOR]

Abstract: Improvement of antifungal agents is a good solution to beat the drug‐resistance problems. In this context, a series of novel bis‐1,2,4‐triazolin‐3‐ones (5i‐t) were designed and synthesized by microwave irradiation (MWI), a convenient and efficient method. An effort was also made to get these bis‐1,2,4‐triazolin‐3‐ones (5i‐t) by one‐pot three‐component reaction (3CR) using 3‐aryl‐5‐methyl‐1,3,4‐oxadiazol‐2(3H)‐one (2a‐b), formamide and dibromo reagent (4c‐h) under microwave irradiation (MWI). In vitro antifungal activity was carried out against six pathogenic fungi. From the results it was observed that the newly synthesized bis‐1,2,4‐triazolin‐3‐ones (5i‐t) have shown excellent activity against all the tested pathogenic fungi with least MIC values in the range of 0.80 μg/ml to 0.20 μg/ml. Particularly, in comparison with the reference drug Fluconazole and mono‐1,2,4‐triazolin‐3‐ones (3a‐b) some of the bis‐1,2,4‐triazolin‐3‐ones (5i, 5j, 5 m, 5p and 5r) have shown broad spectrum of antifungal activity. Further, the molecular docking study has been performed for all the tested compounds with 14α‐demethylase (CYP51) as target enzyme and this study validated the experimental results. Thus, docking study has culminated in the identification of a new class of potent inhibitors of CYP51. The results provide significant information for the future design of more potent antifungal agents. [ABSTRACT FROM AUTHOR]

In this study, drug target was identified using KEGG database and network analysis through Cytoscape software. Designed series of novel benzimidazoles were taken along with reference standard Flibanserin for insilico modeling. The novel 4-(1 H-benzo[ d]imidazol-2-yl)- N-(substituted phenyl)-4-oxobutanamide ( 3a-j) analogs were synthesized and evaluated for their antidepressant activity. Reaction of 4-(1 H-benzo[ d]imidazol-2-yl)-4-oxobutanoic acid ( 1) with 4-(1 H-benzo [ d] imidazol-2-yl)-4-oxobutanoyl chloride ( 2) furnished novel 4-(1 H-benzo [ d] imidazol-2-yl)- N-(substituted phenyl)-4-oxobutanamide ( 3a-j). All the newly synthesized compounds were characterized by IR, 1H- NMR, and mass spectral analysis. The antidepressant activities of synthesized derivatives were compared with standard drug clomipramine at a dose level of 20 mg/kg. Among the derivatives tested, most of the compounds were found to have potent activity against depression. The high level of activity was shown by the compounds 3d, 3e, 3i, and it significantly reduced the duration of immobility time at the dose level of 50 mg/kg. [ABSTRACT FROM AUTHOR]

A wide range of mono- and bis-triazole coumarin hybrids are formed from chromene-2-one derivatives and propargyl ethers employing a Click chemistry modified protocol for Azide-Alkyne cycloadditions. [ABSTRACT FROM AUTHOR]