Exploring the Antimicrobial Potential of Novel 1,2,4−Triazole Conjugates with Pyrazole: Synthesis, Biological Activity and In Silico Docking

In the present study, a new series of 1,2,4-triazole linked pyrazole hybrids (5 a-5 l) were synthesized from dimethyl amino pyrazole (1) in good yield by three-step reaction. The chemical structures of the resulted compounds were thoroughly elucidated using spectral analyses such as IR, ¹H-NMR, ¹³C-NMR, mass spectra and elemental analysis. The target compounds were screened for their antimicrobial activity against the various standard pathogenic Gram-(-ve) (E. coli, P. aeruginosa, K. pneumoniae, A. baumannii), and Gram-(+ve) (S. aureus, S. faecalis) microorganisms. According to the results obtained, in particular, compounds 5 b, 5 f, 5 h and 5 j was effective at inhibiting the antibacterial growth of all the bacteria's, having MIC values ranging 0.983-14.862 mg/mL and compared to moxifloxacin (1.391-22.01 mg mL^-1). The most active compounds were chosen to interact with the DNA gyrase and topoisomerase-IV targets via molecular docking. These selected ligands interacted with 2XCO, 1S16 targets and docked into the active site of amino acids Ala-269, Gly-413, Asn-405, Ser-1182, Thr-1185, His-1186, His-1186, Lys-1189, and Trp-1213. Computational studies were carried out to design the precursor compounds to support the experimental part of the study. The pharmacokinetic properties, stability, and drug-likeness parameters of all target molecules were estimated using SwissADME and PkCSM protocols. The current study used in silico approaches combining e-pharmacophore modeling and structure-based molecular docking of targets to identify antimicrobial agents.