ABSTRACT
Aim: This study was designed to synthesize a novel series of terpyridines with potential antibacterial properties, targeting multidrug resistance. Materials & methods: Terpyridines (4a-h and 6a-c) were synthesized via a one-pot multicomponent reaction using 2,6-diacetylpyridines, benzaldehyde derivatives and malononitrile or ethyl 2-cyanoacetate. The reactions, conducted under grinding conditions with glacial acetic acid, produced high-yield compounds, confirmed by spectroscopic data. Results: The synthesized terpyridines exhibited potent antibacterial activity. Notably, compounds 4d and 4h demonstrated significant inhibition zones against Staphylococcus aureus and Bacillus subtilis, outperforming ciprofloxacin. Conclusion: Molecular docking studies highlighted compounds 4d, 4h and 6c as having strong binding affinity to DNA gyrase B, correlating with their robust antibacterial activity, suggesting their potential as effective agents against multidrug-resistant bacterial strains.
Subject(s)
Anti-Bacterial Agents , Staphylococcus aureus , Molecular Docking Simulation , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , DNA Gyrase/metabolism , Microbial Sensitivity Tests , Topoisomerase II Inhibitors/pharmacology , Topoisomerase II Inhibitors/chemistry , Structure-Activity Relationship , Molecular StructureABSTRACT
A series of pyrazolyl-triazolo[1,5-a]pyrimidines, pyrazolyl-tetrazolo[1,5-a]pyrimidines, pyrazolyl-benzo[4,5]imidazo[1,2-a]pyrimidines and bis-azolopyrimidines were prepared by reaction of pyrazolyl-chalcones or its bis-pyrazolyl-chalcones with the appropriate heterocyclic amines as aminotriazole, aminotetrazole, 2-aminobenzimidazole and 4,6-dimethyl-1H-pyrazolo[3,4-b]pyridin-3-amine by grinding method. The newly synthesized compounds have been characterized on the basis of elemental analysis and spectral data (IR, 1H- and 13C-NMR, Mass). Moreover, the newly synthesized products were screened for their in vitro antibacterial activities and the results showed that compounds 5f and 11d exhibited excellent activities compared with penicillin G and streptomycin as reference drugs.
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/pharmacology , Azo Compounds/pharmacology , Chalcones/chemistry , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Pyrimidines/pharmacology , Anti-Bacterial Agents/chemistry , Azo Compounds/chemical synthesis , Azo Compounds/chemistry , Dose-Response Relationship, Drug , Microbial Sensitivity Tests , Molecular Structure , Pyrimidines/chemical synthesis , Pyrimidines/chemistry , Structure-Activity RelationshipABSTRACT
In the present study, a novel series of 2-(2-(3-aryl-5-substituted-1,3,4-thiadiazol-2(3H)-ylidene)hydrazinyl)-4,4-diphenyl-1H-imidazol-5(4H)-one derivatives were designed and prepared via the reaction of the most versatile, hitherto unreported 2-(5-oxo-4,4-diphenyl-4,5-dihydro-1H-imidazol-2-yl)-N-phenylhydrazinecarbothioamide with the appropriate hydrazonoyl halides. In addition, some thiazole derivatives were prepared. The structures of the newly synthesized compounds were established based on spectroscopic evidences and their alternative syntheses. Some of the newly synthesized compounds have been evaluated for their anticancer activity against a liver carcinoma cell line HEPG2-1. Moreover, their structure-activity relationship (SAR) was explored for further development in this area. The results indicated that many of the tested compounds showed moderate to high anticancer activity with respective to doxorubicin as a reference drug. Consequently, the new synthesized series of thiadiazole-imidazole derivatives are considered as powerful anticancer agents.
Subject(s)
Antineoplastic Agents/pharmacology , Imidazoles/pharmacology , Thiadiazoles/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Hep G2 Cells , Humans , Imidazoles/chemistry , Molecular Structure , Structure-Activity Relationship , Thiadiazoles/chemistryABSTRACT
A novel series of 7,7-diphenyl-1,2-dihydroimidazo[2,1-c][1,2,4]triazin-6(7H)-one 6a-h, were easily prepared via reactions of novel 2-hydrazinyl-4,4-diphenyl-1H-imidazol-5(4H)-one (2) with hydrazonoyl halides 3a-h. In addition, we also examined the reaction of compound 2 with commercially available active methylene compounds to afford new pyrazoles containing an imidazolone moiety, expected to be biologically active. The structures of the synthesized compounds were assigned on the basis of elemental analysis, IR, 1H-NMR and mass spectral data. The antifungal and antibacterial activities of the newly synthesized compounds were evaluated.