Synthesis and evaluation of anti-tubercular activity of 6-(4-substitutedpiperazin-1-yl) phenanthridine analogues.

Autor: Nagesh HN; Department of Chemistry, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, R.R. District, 500078, Andhra Pradesh, India., Suresh N; Department of Chemistry, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, R.R. District, 500078, Andhra Pradesh, India., Mahalakshmi Naidu K; Department of Chemistry, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, R.R. District, 500078, Andhra Pradesh, India., Arun B; Department of Chemistry, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, R.R. District, 500078, Andhra Pradesh, India., Padma Sridevi J; Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, R.R. District, 500078, Andhra Pradesh, India., Sriram D; Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, R.R. District, 500078, Andhra Pradesh, India., Yogeeswari P; Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, R.R. District, 500078, Andhra Pradesh, India., Chandra Sekhar KV; Department of Chemistry, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, R.R. District, 500078, Andhra Pradesh, India. Electronic address: kvgc@hyderabad.bits-pilani.ac.in.
Jazyk: angličtina
Zdroj: European journal of medicinal chemistry [Eur J Med Chem] 2014 Mar 03; Vol. 74, pp. 333-9. Date of Electronic Publication: 2014 Jan 11.
DOI: 10.1016/j.ejmech.2014.01.005
Abstrakt: A series of seventeen new 6-(4-substitutedpiperazin-1-yl)phenanthridine derivatives were designed, synthesized, and evaluated for their anti-tubercular activity against Mycobacterium tuberculosis H37Rv by Microplate Alamar Blue Assay and most active compounds were tested for cytotoxicity studies against mouse macrophage cell lines (RAW264.7). Among the tested compounds, ten compounds exhibited significant activity against the growth of M. tuberculosis (MIC ranging from 1.56 to 6.25 μg/mL). In particular, compounds 5e, 5j and 5k displayed excellent activity against the growth of M. tuberculosis (MIC 1.56 μg/mL). The selectivity index values were found to be >25, indicating compounds likeliness in drug development for tuberculosis. The structure of 5k is substantiated by X-ray crystallographic study. Structure-activity correlation indicates the importance of substituent at 4th position of piperazinyl phenanthridine ring.
(Copyright © 2014 Elsevier Masson SAS. All rights reserved.)
Databáze: MEDLINE
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