Design, synthesis of benzocoumarin-pyrimidine hybrids as novel class of antitubercular agents, their DNA cleavage and X-ray studies

作者：Reddy Dinesh S; Hosamani Kallappa M^*; Devarajegowda Hirihalli C

来源：European Journal of Medicinal Chemistry, 2015, 101: 705-715.

DOI：10.1016/j.ejmech.2015.06.056

• Benzocoumarin
• Pyrimidine
• Antitubercular activity
• Cytotoxicity
• X-ray structure
• DNA cleavage

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 mu g/mL. Among them, compound (1b) possessed excellent activity (MIC 0.05 mu g/mL) against M.tb H(37)Rv, 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.

• 出版日期2015-8-28