Design, synthesis and anti-mycobacterial activity of 1,2,3,5-tetrasubstituted pyrrolyl-N-acetic acid derivatives

• A novel tetrasubstituted-1H-pyrrol-1-yl-N-acetic acid derivatives were prepared.
• Products were screened against Mycobacterium tuberculosis H37Rv and Mycobacterium smegmatis.
• The cytotoxicity of TB active compounds were evaluated against HEK-293T cell line.
• 5n, 5q & 5r showed significant anti-TB activity against M. tuberculosis H37Rv.
• 5d, 5g, 5i & 5j exhibited moderate activity against M. smegmatis.

A novel synthesis of highly substituted pyrrole-N-acetic derivatives is described through the coupling of 1,4-diketones with amino acids following Paal–Knorr's approach. These pyrrole-N-acetic acid derivatives are found to exhibit potent anti-mycobacterial activity against Mycobacterium smegmatis and Mycobacterium tuberculosis strain H37Rv. In particular, 5n, 5q & 5r are found to display excellent anti-mycobacterial activity against M. tuberculosis strain H37Rv with MIC values in the range of 2.97 μM. Conversely, these compounds showed low cytotoxicity (selectivity index: >16.83) against HEK-293T cell line.

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