Naik, S.Dinesha, P.Udayakumar, D.2026-02-032024Molecular Diversity, 2024, 28, 6, pp. 4221-423913811991https://doi.org/10.1007/s11030-024-10812-0https://idr.nitk.ac.in/handle/123456789/20821In this study, we present a novel series of (E)-4-((2-(pyrazine-2-carbonyl) hydrazineylidene)methyl)phenyl benzenesulfonate (T1-T8) and 4-((E)-(((Z)-amino(pyrazin-2-yl)methylene)hydrazineylidene)methyl)phenyl benzenesulfonate (T9-T16) derivatives which exert their inhibitory effects on decaprenylphosphoryl-?-D-ribose 2'-epimerase (DprE1) through the formation of hydrogen bonds with the pivotal active site Cys387 residue. Their effectiveness against the M. tuberculosis H37Rv strain was examined and notably, three compounds (namely T4, T7, and T12) exhibited promising antitubercular activity, with a minimum inhibitory concentration (MIC) of 1.56 µg/mL. The target compounds were screened for their antibacterial activity against a range of bacterial strains, encompassing S. aureus, B. subtilis, S. mutans, E. coli, S. typhi, and K. pneumoniae. Additionally, their antifungal efficacy against A. fumigatus and A. niger also was scrutinized. Compounds T6 and T12 demonstrated significant antibacterial activity, while compound T6 exhibited substantial antifungal activity. Importantly, all of these active compounds demonstrated exceedingly low toxicity without any adverse effects on normal cells. To deepen our understanding of these compounds, we have undertaken an in silico analysis encompassing Absorption, Distribution, Metabolism, and Excretion (ADME) considerations. Furthermore, molecular docking analyses against the DprE1 enzyme was conducted and Density-Functional Theory (DFT) studies were employed to elucidate the electronic properties of the compounds, thereby enhancing our understanding of their pharmacological potential. © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2024.4 e z amino pyrazin 2 yl methylene hydrazineylidene methyl phenyl 2 trifluoromethyl benzenesulfonate4 e z amino pyrazin 2 yl methylene hydrazineylidene methyl phenyl 4 bromo benzenesulfonate4 e z amino pyrazin 2 yl methylene hydrazineylidene methyl phenyl 4 chloro benzenesulfonate4 e z amino pyrazin 2 yl methylene hydrazineylidene methyl phenyl 4 fluoro benzenesulfonate4 e z amino pyrazin 2 yl methylene hydrazineylidene methyl phenyl 4 methoxy benzenesulfonate4 e z amino pyrazin 2 yl methylene hydrazineylidene methyl phenyl 4 methyl benzenesulfonate4 e z amino pyrazin 2 yl methylene hydrazineylidene methyl phenyl 4 trifluoromethyl benzenesulfonate4 e z amino pyrazin 2 yl methylene hydrazineylidene methyl phenyl benzenesulfonate derivative4e z amino pyrazin 2 yl methylene hydrazineylidene methyl phenyl benzene sulfonatechemical compoundciprofloxacine 4 2 pyrazine 2 carbonyl hydrazineylidene methyl phenyl 2 trifluoromethyl benzenesulfonatee 4 2 pyrazine 2 carbonyl hydrazineylidene methyl phenyl 4 bromobenzene sulfonatee 4 2 pyrazine 2 carbonyl hydrazineylidene methyl phenyl 4 chlorobenzene sulfonatee 4 2 pyrazine 2 carbonyl hydrazineylidene methyl phenyl 4 fluorobenzene sulfonatee 4 2 pyrazine 2 carbonyl hydrazineylidene methyl phenyl 4 methoxybenzene sulfonatee 4 2 pyrazine 2 carbonyl hydrazineylidene methyl phenyl 4 methylbenzene sulfonatee 4 2 pyrazine 2 carbonyl hydrazineylidene methyl phenyl 4 trifluoromethyl benzenesulfonatee 4 2 pyrazine 2 carbonyl hydrazineylidene methyl phenyl benzenesulfonatee 4 2 pyrazine 2 carbonyl hydrazineylidene methyl phenyl benzenesulfonate derivativepyrazinamidepyrazine 2 carbohydrazidestreptomycinunclassified drugz pyrazine 2 carbohydrazonamidealcohol dehydrogenasebacterial proteinbenzenesulfonic acidbenzenesulfonic acid derivativeDprE1 protein, Mycobacterium tuberculosispyrazine derivativetuberculostatic agentanimal cellantibacterial activityantifungal activityantimicrobial activityantineoplastic activityArticleAspergillus fumigatusAspergillus nigerBacillus subtiliscarbon nuclear magnetic resonancecell viabilitycontrolled studycytotoxicitydensity functional theorydrug analysisdrug designEscherichia coligrowth inhibitionKlebsiella pneumoniaeminimum inhibitory concentrationMTT assayMycobacterium tuberculosisnonhumanproton nuclear magnetic resonanceStaphylococcus aureusstructure activity relationtuberculosisVero cell linezone of inhibitionchemistrydrug effectdrug therapyenzymologymicrobial sensitivity testmolecular dockingAlcohol OxidoreductasesAntitubercular AgentsBacterial ProteinsBenzenesulfonatesDrug DesignMicrobial Sensitivity TestsMolecular Docking SimulationPyrazinesStructure-Activity RelationshipTuberculosis