title: Novel amide and sulphonamide derivatives of 6-(piperazin-1-yl)phenanthridine as potent Mycobacterium tuberculosis H37Rv inhibitors.
abstract: 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.
authors.affiliation: Department of Chemistry, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawahar Nagar, Shamirpet Mandal, Hyderabad 500 078, Telangana, India.
authors.forename: Kalaga Mahalakshmi
authors.initials: KM
authors.lastname: Naidu
authors.affiliation: Department of Chemistry, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawahar Nagar, Shamirpet Mandal, Hyderabad 500 078, Telangana, India.
authors.forename: Hunsur Nagendra
authors.initials: HN
authors.lastname: Nagesh
authors.affiliation: Department of Chemistry, Banaras Hindu University, Varanasi 221 005, India.
authors.forename: Manjeet
authors.initials: M
authors.lastname: Singh
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawahar Nagar, Shamirpet Mandal, Hyderabad 500 078, Telangana, India.
authors.forename: Dharmarajan
authors.initials: D
authors.lastname: Sriram
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawahar Nagar, Shamirpet Mandal, Hyderabad 500 078, Telangana, India.
authors.forename: Perumal
authors.initials: P
authors.lastname: Yogeeswari
authors.affiliation: 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.
authors.forename: Kondapalli Venkata
authors.initials: KV
authors.lastname: Gowri Chandra Sekhar
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006867:Hydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000201:enzymology; D010617:Phenanthridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: C000603214:6-(piperazin-1-yl)phenanthridine; D000577:Amides; D000995:Antitubercular Agents; D004791:Enzyme Inhibitors; D010617:Phenanthridines; D010879:Piperazines; D006867:Hydrolases; C527647:HsaD protein, Mycobacterium tuberculosis
keywords: Antimycobacterial activity; Mycobacterium tuberculosis; Phenanthridine; Piperazine sulphonamide; Single crystal XRD