Synthesis of N-substituted indole derivatives as potential antimicrobial and antileishmanial agents

Abstract

Leishmaniasis and microbial infections are two of the major contributors to global mortality and morbidity rates. Hence, development of novel, effective and safer antileishmanial and antimicrobial agents having reduced side effects are major priority for researchers. Two series of N-substituted indole derivatives i.e. N-substituted indole based chalcones (12a-g) and N-substituted indole based hydrazide-hydrazones (18a-g, 19a-f, 21 a-g) were synthesized. The synthesized compounds were characterized by ¹H NMR, ¹³C NMR, Mass and FT-IR spectral data. Further these derivatives were evaluated for their antimicrobial potential against Escherichia coli, Bacillus subtilis, Pseudomonas putida and Candida viswanathii, and antileishmanial potential against promastigotes of Leishmania donovani. Compounds 18b, 18d and 19d exhibited significant activity with an IC₅₀ of 0.19 ± 0.03 µM, 0.14 ± 0.02 µM and 0.16 ± 0.06 µM against B. subtilis which was comparable to chloramphenicol (IC₅₀ of 0.25 ± 0.03 µM). Compounds 12b and 12c exhibited an IC₅₀ of 24.2 ± 3.5 µM and 21.5 ± 2.1 µM in the antileishmanial assay. Binding interactions of indole based hydrazide-hydrazones were studied with nitric oxide synthase in silico in order to understand the structural features responsible for activity.

Keywords: Antileishmanial activity; Antimicrobial activity; Chalcones; Hydrazide-hydrazones; Indole.