title: 2-Butyl-4-chloroimidazole based substituted piperazine-thiosemicarbazone hybrids as potent inhibitors of Mycobacterium tuberculosis.
abstract: Here a series of 2-butyl-4-chloroimidazole based substituted piperazine-thiosemicarbazone hybrids were designed by combining three different pharmacophoric fragments in single molecular architecture. 2-Butyl-4-chloro-1-(3-(4-substituted)piperazin-1-yl)propyl)-1H-imidazole-5-carbaldehydes (4a-p) prepared by reacting carboxaldehyde 2 with N-alkyl piperazines 3a-p which were condensed with thiosemicarbazine to give desired compounds 5a-p in very good yields. Among all sixteen compounds screened for in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv (MTB), two compounds (E)-2-((2-butyl-4-chloro-1-(3-(4-(o-tolyl) piperazin-1-yl)propyl)-1H-imidazol-5-yl)methylene)hydrazinecarbothioamide 5e and (E)-2-((2-butyl-4-chloro-1-(3-(4-(2-methoxyphenyl)piperazin-1-yl)propyl)-1H-imidazol-5-yl)methylene) hydrazine carbothioamide 5f were found to be the most potent antitubercular agents (MIC: 3.13 μg/mL) with low toxicity profile.
authors.affiliation: Organic Chemistry Division-II (CPC Division), CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, Telangana, India.
authors.forename: Anvesh
authors.initials: A
authors.lastname: Jallapally
authors.affiliation: Organic Chemistry Division-II (CPC Division), CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, Telangana, India.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Addla
authors.affiliation: Medicinal Chemistry and Antimycobacterial Research Laboratory, Pharmacy Group, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad 500078, Telangana, India.
authors.forename: Perumal
authors.initials: P
authors.lastname: Yogeeswari
authors.affiliation: Medicinal Chemistry and Antimycobacterial Research Laboratory, Pharmacy Group, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad 500078, Telangana, India.
authors.forename: Dharmarajan
authors.initials: D
authors.lastname: Sriram
authors.affiliation: Organic Chemistry Division-II (CPC Division), CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, Telangana, India; Academy of Scientific and Innovative Research, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, Telangana, India. Electronic address: kantevari@yahoo.com.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Kantevari
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D015195:Drug Design; D007093:Imidazoles; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D000077489:Piperazine; D010879:Piperazines / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013882:Thiosemicarbazones / Q000737:chemistry*; D014230:Triazoles / Q000494:pharmacology
chemical_list: D000995:Antitubercular Agents; D007093:Imidazoles; D010879:Piperazines; D013882:Thiosemicarbazones; D014230:Triazoles; D000077489:Piperazine; C029899:imidazole
keywords: Antimycobacterial activity; Imidazole; Molecular hybridization; Mycobacterium tuberculosis; Thiosemicarbazide