SYNTHESIS, CHARACTERIZATION AND ANTIMICROBIAL EVALUATION OF NOVEL 1, 4-DISUBSTITUTED PIPERAZINE DERIVATIVES

Abstract

Piperazine is a heterocyclic compounds which have two nitrogen atoms at opposite positions in the six membered ring were reported to have extensive applications in various medical and industrial fields. In this study six novel 1,4-disubstituted piperazine derivatives 4a-c (benzyl piperazine hybrid ) and 5a-c (indole piperazine hybrid ) were synthesized by using bromination of alcohols and by nucleophilic substitution of various piperazine derivatives with benzyl bromides and 3-bromo ethyl indole to get the target compounds with a yield of 52-85%. Structures of the synthesized compounds were elucidated by using IR and one-dimensional NMR techniques ( 1H-NMR, 13C-NMR and DEPT-135). All compounds were assayed in vitro for their antimicrobial activities against Staphylococcus aureus (Gram-positive) and Escherichia coli (Gram-negative) bacteria and antifungal activities were also studied against fungi like Aspergillus niger and Aspergillus flavus using the paper disc diffusion method. Chloramphenicol and carbendazim were used as a standard drug for the antibacterial and antifungal activities, respectively. The compound 5a (3-(2-(4-phenylpiperazin-1-yl) ethyl)-1H-indole) showed a greater ability of inhibition against Gram-positive bacteria (Staphylococcus aureus) than the other compounds. The compound 4c (1-benzyl-4-(pyridine-2-yl) piperazine) showed a greater ability of inhibition against Gram-negative bacteria (Escherichia coli) than the other compounds. In the antifungal activity, among the newly synthesized 1, 4- disubstituted piperazine derivatives, compound 4c (1-benzyl-4-(pyridine-2-yl) piperazine) was the most active compound against both Aspergillus niger and Aspergillus flavus at a dose of 20 μg/mL. All the newly synthesized 1, 4- disubstituted piperazine derivatives did not show any inhibition zone against Aspergillus flavus at a dose of 10 μg/mL. In the antitubercular activity, Compound 5c was significantly inhibited the growth of Mtb H37Rv with MIC of 1.56 μg/mL, which was better than the standard drug Ethambutol (3.25 μg/mL).