Synthesis and structural study of some N-acyl-4-allylsemicarbazides and the product of their cyclization with a potential antimicrobial activity

Abstract In this paper semicarbazide (2a-2h) and 1,2,4-trazole (3a-3h) derivatives with allyl group were synthesized. All compounds were tested in vitro for their antimicrobial activity showing different activity to E. coli, S. aureus, S. epidermidis, M. smegmatis, M. phlei and M. tuberculosis H37Ra. The antimicrobial activity is showed 2g against S. epidermidis, 3g against E. coli and S. epidermidis and 3h against E. coli. The crystal structure of determinations of 2b, 2d, 3b, 3c and 3e were undertaken in order to confirm the synthesis pathway and identification of their tautomeric forms in the crystalline state. Theoretical calculations showed that the physico-chemicals (logP) and electronic properties (MEP distribution, energy localization of HOMO and LUMO orbitals) are related to observed antimicrobial activity of investigated compounds. The molecular docking study carried out for the most active against M. tuberculosis compound 3b using the M. tuberculosis cytochrome P450 CYP121 showed that this compound binds to the active site of P450 by hydrogen bonds via water molecule with the amino acid residue of Met86A and molecule of hem.