SYNTHESIS, CHARACTERIZATION AND ANTIMICROBIAL EVALUATION OF NOVEL (2-FURANYLMETHYL)PIPERAZINE DERIVATIVES

Abstract

The worldwide problem of microbial resistance has drawn utmost attention for organic and medicinal chemists because of failure of currently available antimicrobial therapy against microbial infections. One of the most viable options to tackle the growing resistance to the antimicrobial drugs is the synthesis of hybrid molecules. In the present study, a total of four furan-piperazine hybrid compounds were synthesized by the reductive amination process (first by synthesizing an important reagent sodium triacetoxyborohydride from sodium borohydride and acetic acid) as a single step with a yield of 74-85% and characterized by various spectroscopic techniques viz 1H NMR, 13C NMR and HRMS (ESI+). 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. In particular, compounds substituted with 2-fluorophenyl groups were shown significant inhibitory activities against the tested bacterial species. For the anti-fungal activity, compound (X-5-5-1) bearing 5-nitro on furan and 2-pyridinyl on the piperazine ring was the most active compounds against Fusarium moniliformale, and compound (X-5-1-1) having unsubstituted furan and 2-fluorophenyl substituent on the piperazine ring revealed good inhibitory activity against Aspergillus niger. All the synthesized compounds were also evaluated against Mycobacterium tuberculosis H37Rv strains. Interestingly, compound 1-(2-fluorophenyl)-4-(furan-2-ylmethyl)piperazine (X-5-1-1) and 1(furan-2-ylmethyl)-4-(pyridin-2-yl)piperazine(X-5-1-2)were found to be the most potent compound in the treatment of mycobacterial strains. These studies demonstrate that unsubstituted furan rings posses better antitubercular activity than those having 5-nitro substituent on furan rings of 1-(furan-2-ylmethyl)piperazine derivatives. The potent activity and straightforward synthesis of these 1-(2-furanylmethyl)piperazines suggest that they are potential candidates for the development of new antimicrobial and antitubercular agents.