Indole-fused spirochromenes as potential anti-tubercular agents: design, synthesis and in vitro evaluation

Abstract

As part of an ongoing effort to develop new anti-tubercular agents, a series of novel indole-fused spirochromene hybrids (7a-l) were efficiently synthesized in excellent yields by the popular 'Fisher-Indole synthesis' approach. The structure elucidation of the target compounds was carried out by different spectral techniques including ¹H-NMR, ¹³C-NMR, ESI Mass, and FTIR analysis. Additionally, the proposed structure of 7i was proved by single-crystal X-ray analysis. These compounds (7a-l) were screened for in vitro anti-tubercular activity against Mycobacterium tuberculosis H37Rv (ATCC 27294) strain. The results showed that most of the targets exhibited promising antimycobacterial activity with MICs of 1.56-6.25 μg/mL and weak cytotoxicity (19.93-32.16% at 50 μg/mL). Among them, compound 7l was found to be the most active compound (MIC of 1.56 μg/mL) with a good safety profile (32.16% at 50 μg/mL).

Keywords: Indole; Indole-fused spirochromene; Mycobacterium tuberculosis; Spirochromene; X-ray crystal.