Synthesis of novel antipyrine-azole-S-alkyl derivatives antimicrobial activity, molecular docking, and computational studies

In this investigation, we synthesized the newly antipyrine-azole-S-alkyl and their reduction derivatives that were screened for their antimicrobial activity and compared them with molecular docking and computational Studies. The nucleophilic substitution reaction between antipyrine-azole derivatives 1a, 1b and (2,4-dichlorophenyl) acetyl chloride ( 2 ) in presence of Na metal to afforded the corresponding 2-(2,4-dichlorophenyl)-2-oxoethyl)thio)-4H-1,2,4-triazol-3-yl)methyl)amino)-1,5-dimethyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one derivatives 3a, 3b in excellent yield. The reduction process of compounds 3a,3b were utilized via NaBH4 act as reducing agent which convert the C = O group to OH group to afford the corresponding 2-(2,4-dichlorophenyl)-2-hydroxyethyl)thio)-4H-1,2,4-triazol-3-yl)methyl)amino)-1,5-dimethyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one derivatives 4a, 4b. The investigated compounds were exhibited against in vitro antimicrobial activity. Compound 3a was determined to be the most effective against all strains. In addition, it was observed that compound 4a showed very good antitubercular activity ( Mycobacterium smegmatis ATCC607) and showed equivalent activity to Staphylococcus aureus ATCC 25923 against the standard drug from gram-positive bacteria. Compound 3b with allyl group in its structure was found to be effective against Pseudomonas aeruginosa ATCC 27853, one of the gram-negative bacteria. Furthermore, molecular docking studies were carried out on one of the investigated compounds with (PDB ID:3t88), (PDB ID:2wje), (PDB ID:4ynt), and (PDB ID:1tgh), which attached with different proteins with different energies and short bond distance. Furthermore, the comprehensive theoretical and physical characterization studies of compounds 3a, 3b,4a, and 4b were examined via DFT/ B3LYP/6-31 G (d) level to elucidate their activities. (C)& nbsp;2022 Elsevier B.V. All rights reserved.