Synthesis, characterization, and in vitro antibacterial activity of some new pyridinone and pyrazole derivatives with some in silico ADME and molecular modeling study

Abstract A new series of pyridine-2-one and pyrazole derivatives were designed synthesized based on cyanoacrylamide containing 2,4-dichlro aniline 6-methyl 2-amino pyridine as an aryl group. Condensation 3a–d with different active methylene (malononitrile, ethyl cyanoacetate cyanoacetamide, acetoacetate) in the presence piperidine basic catalyst afforded corresponding pyridinone 4a–c , 5 9 13 . Furthermore, reaction bi-nucleophile hydrazine hydrate thiosemicarbazide 14a,b 16 The newly confirmed established elemental analysis spectra data (IR, 1 H NMR, C mass). vitro antibacterial activity was evaluated against four bacterial strains weak to good activity. Moreover, results indicated that most 3a 4a 4b might lead agents, especially B. subtilis P. vulgaris DFT calculations performed estimate its geometric structure electronic properties. In addition, further for silico physicochemical, drug-likeness, toxicity prediction. These obeyed all Lipinski’s Veber’s rules without any violation displayed non-immunotoxin, non-mutagenic, non-cytotoxic. Molecular docking simulation inside site Topoisomerase IV (PDB:3FV5). It binding energy ranging from -14.97 kcal/mol -18.86 hydrogen bonding arene–cation interaction. Therefore, these suggested be agents via topoisomerase inhibitor. Graphical abstract