title: Design, synthesis of benzocoumarin-pyrimidine hybrids as novel class of antitubercular agents, their DNA cleavage and X-ray studies.
abstract: A series of 2-(2-(4-fluorobenzyl)-6-(substituted phenyl) pyrimidin-4-yl)-3H-benzo[f]chromen-3-one derivatives (1a-1o) were selectively prepared in high yields under microwave irradiation. The synthesized compounds were characterized by elemental and spectroscopic analysis; in addition the structures of compound (1a), (1b) and (1j) were elucidated by the X-ray diffraction technique. Compounds (1a-1o) were evaluated for their in-vitro antitubercular activity while the most active compounds were further subjected for their cytotoxicity and DNA cleavage study. Results revealed that most of the tested compounds displayed potent antitubercular activity with MIC in the range 0.05-2.81 μg/mL. Among them, compound (1b) possessed excellent activity (MIC 0.05 μg/mL) against M.tb H37Rv strain and exhibited low level of cytotoxicity against Vero cells, which suggested compound (1b) is a promising lead for subsequent investigation in search of new antitubercular agents. DNA cleavage by gel electrophoresis method revealed that compounds (1b, 1g, 1k and 1n) were found to cleave the DNA completely.
authors.affiliation: Department of Studies in Chemistry, Karnatak University, Dharwad 580003, India.
authors.forename: Dinesh S
authors.initials: DS
authors.lastname: Reddy
authors.affiliation: Department of Studies in Chemistry, Karnatak University, Dharwad 580003, India. Electronic address: dr_hosamani@yahoo.com.
authors.forename: Kallappa M
authors.initials: KM
authors.lastname: Hosamani
authors.affiliation: Department of Physics, Yuvaraja's College, University of Mysore, Mysore 570005, India.
authors.forename: Hirihalli C
authors.initials: HC
authors.lastname: Devarajegowda
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D003374:Coumarins / Q000737:chemistry* / Q000494:pharmacology; D018360:Crystallography, X-Ray; D053837:DNA Cleavage / Q000187:drug effects*; D004269:DNA, Bacterial / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000254:growth & development; D011743:Pyrimidines / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014709:Vero Cells
chemical_list: D000995:Antitubercular Agents; D003374:Coumarins; D004269:DNA, Bacterial; D011743:Pyrimidines; C030986:pyrimidine
keywords: Antitubercular activity; Benzocoumarin; Cytotoxicity; DNA cleavage; Pyrimidine; X-ray structure