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

Abstract

Piperazine is a heterocyclic compound which has two nitrogen atoms at opposite positions in the six membered ring with extensive applications in various medical and industrial fields. In this study four novel 1,4-disubstituted piperazine derivatives (P1-4) were synthesized by using the process reduction of aldehyde, bromination of alcohol and by nucleophilic substitution of piperazine derivatives with various alkyl bromides to get the target compounds. Structures of the synthesized compounds were elucidated by using IR and one-dimensional NMR techniques ( 1H-NMR, 13C-NMR and DEPT-135). All products 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 Aspargillus niger and Fusarium moniliformale using the paper disc diffusion method. Chloramphenicol and Tilt were used as a reference drug for the antibacterial and antifungal activities, respectively. The compound 3-((4-(pyridin-2-yl)piperazine-1-yl) methyl)-1H-indole (P3) showed a greater ability of inhibition against both tested bacteria than the other compounds. In the antifungal activity, the nitrobenzyl substituted piperazine derivative, 1-(2-nitrobenzyl)-4-(pyridin-2-yl)piperazine (P1) revealed good inhibitory activity against the tested fungal species. The pyridinyl group which is incorporated in the piperazine ring has showed a marked effect on the activity of the parent compound, while the halide substituted phenyl group showed less antimicrobial effect. In the antitubercular activity, fluorophenyl substituted piperazine derivatives (P2 and P4) were the most potent with MIC of 1.56 µg/mL against the Mtb strain. The compounds exhibited significant antifungal, antitubercular and moderate antibacterial activities. on the basis of their activity, these compounds can be identified as viable leads for further studies.