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

Lakshmi Reddy Pagadala; Lakshmi Devi Mukkara; Satyanarayana Singireddi; Ashita Singh; Veera Reddy Thummaluru; Padma Sridevi Jagarlamudi; Raja Sekhar Guttala; Yogeeswari Perumal; Sriram Dharmarajan; Suryanarayana Murty Upadhyayula; Ramesh Ummanni; Venkata Subba Reddy Basireddy; Narender Ravirala

doi:10.1016/j.ejmech.2014.06.075

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

Eur J Med Chem. 2014 Sep 12:84:118-26. doi: 10.1016/j.ejmech.2014.06.075. Epub 2014 Jul 1.

Affiliations

¹ Crop Protection Chemicals, Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500 007, India.
² Department of Chemistry, Vikrama Simhapuri University, Nellore 524001, India.
³ Chemical Biology, Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500 007, India.
⁴ Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, India.
⁵ Biology Division Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500 007, India.
⁶ Natural Product Chemistry, Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500 007, India.
⁷ Crop Protection Chemicals, Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500 007, India. Electronic address: ravindra@iict.res.in.

PMID: 25016370
DOI: 10.1016/j.ejmech.2014.06.075

Abstract

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.

Keywords: Anti-mycobacterial activity; Paal–Knorr pyrrole synthesis; Stetter reaction.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetates / chemical synthesis
Acetates / chemistry
Acetates / pharmacology*
Anti-Bacterial Agents / chemical synthesis
Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology*
Dose-Response Relationship, Drug
Drug Design*
Microbial Sensitivity Tests
Molecular Structure
Mycobacterium tuberculosis / drug effects*
Pyrroles / chemical synthesis
Pyrroles / chemistry
Pyrroles / pharmacology*
Structure-Activity Relationship

Substances

Acetates
Anti-Bacterial Agents
Pyrroles