Novel (2-Oxoindolin-3-ylidene)methyl)-1H-pyrazole and their fused derivatives: Design, synthesis, antimicrobial evaluation, DFT, chemical approach, in silico ADME and molecular docking studies

A series of novel (2-oxoindolin-3-ylidene)methyl)-1H-pyrazole and their fused derivatives bearing oxindole moiety have been designed and successfully synthesized to and spectroscopically well characterized screen their., synthesized. evaluated for their in vitro antimicrobial activity against human pathogenic strains and investigated by different in silico methods. Compounds 11a with MIC values of 16.98 mM (S. aureus and P. aeruginosa) and 19.81 mM (B. subtilis, E. coli and K. pneumoniae) exhibited moderate antibacterial potency with respect to the reference drug, chloramphenicol. Moreover, B. subtilis was found to be the most susceptible bacterial strain with MICs value in the range of 18.08–32.58 mM. Structure–activity relationship (SAR) study revealed that the antibacterial potency has been improved by the incorporation of triazine ring. Furthermore, the activity and the stability of the tested compounds examined by Density Functional Theory (DFT) calculation were carried out with the Becke3-Lee-Yang-parr (B3LYP) level using 6–31G(d,p) basis set, to obtain the ground state optimized geometry. Additionally, docking studies were performed towards the most promising compound, 11a in the active site of topoisomerase II DNA gyrase from S. aureus, tyrosyl-tRNA synthetase from S. aureus and secreted aspartic proteinase (SAP2) from C. albicans revealing strong interactions. Drug-likeness and pharmacokinetics parameters reveled that 11a exhibited favorable ADME properties. Therefore, 11a serve as a good lead for developing new potential antimicrobial agents after considering further investigations.