Reddy Dinesh S, Hosamani Kallappa M, Devarajegowda Hirihalli C
Department of Studies in Chemistry, Karnatak University, Dharwad 580003, India.
Department of Studies in Chemistry, Karnatak University, Dharwad 580003, India.
Eur J Med Chem. 2015 Aug 28;101:705-15. doi: 10.1016/j.ejmech.2015.06.056. Epub 2015 Jul 16.
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.
在微波辐射下，以高产率选择性地制备了一系列2-(2-(4-氟苄基)-6-(取代苯基)嘧啶-4-基)-3H-苯并[f]色烯-3-酮衍生物(1a - 1o)。通过元素分析和光谱分析对合成的化合物进行了表征；此外，通过X射线衍射技术阐明了化合物(1a)、(1b)和(1j)的结构。对化合物(1a - 1o)的体外抗结核活性进行了评估，同时对活性最强的化合物进一步进行了细胞毒性和DNA裂解研究。结果表明，大多数测试化合物显示出强效抗结核活性，MIC范围为0.05 - 2.81μg/mL。其中，化合物(1b)对结核分枝杆菌H37Rv菌株具有优异的活性(MIC 0.05μg/mL)，并且对Vero细胞表现出低水平的细胞毒性，这表明化合物(1b)是后续寻找新型抗结核药物研究的有前景的先导化合物。凝胶电泳法进行的DNA裂解显示，发现化合物(1b、1g、1k和1n)能完全裂解DNA。
