Synthesis and evaluation of anti-tubercular activity of 6-(4-substitutedpiperazin-1-yl) phenanthridine analogues.
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.
Department of Chemistry, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, R.R. District, 500078, Andhra Pradesh, India.
Hunsur Nagendra
HN
Nagesh
Department of Chemistry, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, R.R. District, 500078, Andhra Pradesh, India.
Narva
N
Suresh
Department of Chemistry, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, R.R. District, 500078, Andhra Pradesh, India.
Kalaga
K
Mahalakshmi Naidu
Department of Chemistry, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, R.R. District, 500078, Andhra Pradesh, India.
Boyineni
B
Arun
Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, R.R. District, 500078, Andhra Pradesh, India.
Jonnalagadda
J
Padma Sridevi
Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, R.R. District, 500078, Andhra Pradesh, India.
Dharmarajan
D
Sriram
Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, R.R. District, 500078, Andhra Pradesh, India.
Perumal
P
Yogeeswari
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.
Kondapalli Venkata Gowri
KV
Chandra Sekhar
D000818:Animals; D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002460:Cell Line; D018360:Crystallography, X-Ray; D008264:Macrophages / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000254:growth & development; D010617:Phenanthridines / Q000138:chemical synthesis* / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization
D000995:Antitubercular Agents; D010617:Phenanthridines
Anti-tubercular activity; Microwave synthesis; Phenanthridine; Piperazine; X-ray crystallography