Novel amide and sulphonamide derivatives of 6-(piperazin-1-yl)phenanthridine as potent Mycobacterium tuberculosis H37Rv inhibitors.

Autor: Naidu KM; Department of Chemistry, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawahar Nagar, Shamirpet Mandal, Hyderabad 500 078, Telangana, India., Nagesh HN; Department of Chemistry, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawahar Nagar, Shamirpet Mandal, Hyderabad 500 078, Telangana, India., Singh M; Department of Chemistry, Banaras Hindu University, Varanasi 221 005, India., Sriram D; Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawahar Nagar, Shamirpet Mandal, Hyderabad 500 078, Telangana, India., Yogeeswari P; Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawahar Nagar, Shamirpet Mandal, Hyderabad 500 078, Telangana, India., Gowri Chandra Sekhar KV; Department of Chemistry, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawahar Nagar, Shamirpet Mandal, Hyderabad 500 078, Telangana, India. Electronic address: kvgc@hyderabad.bits-pilani.ac.in.
Jazyk: angličtina
Zdroj: European journal of medicinal chemistry [Eur J Med Chem] 2015 Mar 06; Vol. 92, pp. 415-26. Date of Electronic Publication: 2015 Jan 09.
DOI: 10.1016/j.ejmech.2015.01.013
Abstrakt: A series of thirty three novel 6-(piperazin-1-yl)phenanthridine amide and sulphonamide analogues were synthesized, characterized and screened for their in vitro antimycobacterial activity against Mycobacterium tuberculosis (MTB) H37Rv strain. These compounds exhibited minimum inhibitory concentration (MIC) between 1.56 and ≥50 μg/mL. Out of these derivatives, few compounds 6l, 6r, 7b, 7f, 7g and 7k exhibited moderate activity (MIC = 6.25 μg/mL) and compounds 6b, 6e, 6k, 6n, 7h, 7i and 7n displayed good activity (MIC = 3.13 μg/mL), whereas compounds 6m, 6s and 7d exhibited excellent anti-tubercular activity (MIC = 1.56 μg/mL). In addition, MTT assay was accomplished on the active analogues of the series against mouse macrophage (RAW 264.7) cells to evaluate the toxicity profile of the newly synthesized compounds and selectivity index of the compounds was determined. Additionally, compounds 6b and 7d were docked to the ATPase domain of M. tuberculosis GyrB protein to know the interaction profile and structures of compounds 6b and 7d were further substantiated through single crystal XRD.
(Copyright © 2015 Elsevier Masson SAS. All rights reserved.)
Databáze: MEDLINE
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