Scott Fraser J, Nichol Ryan J O, Khalaf Abedawn I, Giordani Federica, Gillingwater Kirsten, Ramu Soumya, Elliott Alysha, Zuegg Johannes, Duffy Paula, Rosslee Michael-Jon, Hlaka Lerato, Kumar Santosh, Ozturk Mumin, Brombacher Frank, Barrett Michael, Guler Reto, Suckling Colin J
School of Chemistry, University of Lincoln, Brayford Pool, Lincoln, Lincolnshire, LN6 7TS, United Kingdom.
WestCHEM Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, United Kingdom.
Eur J Med Chem. 2017 Aug 18;136:561-572. doi: 10.1016/j.ejmech.2017.05.039. Epub 2017 May 17.
This study details the synthesis and biological evaluation of a collection of 19 structurally related Minor Groove Binders (MGBs), derived from the natural product distamycin, which were designed to probe antifungal and antimycobacterial activity. From this initial set, we report several MGBs that are worth more detailed investigation and optimisation. MGB-4, MGB-317 and MGB-325 have promising MICs of 2, 4 and 0.25 μg/mL, respectively, against the fungus C. neoformans.MGB-353 and MGB-354 have MICs of 3.1 μM against the mycobacterium M. tuberculosis. The selectivity and activity of these compounds is related to their physicochemical properties and the cell wall/membrane characteristics of the infective agents.
本研究详细介绍了一系列19种结构相关的小沟结合剂（MGBs）的合成及生物学评价，这些化合物衍生自天然产物偏端霉素，旨在探究其抗真菌和抗分枝杆菌活性。从这一初始化合物组中，我们报告了几种值得更深入研究和优化的MGBs。MGB - 4、MGB - 317和MGB - 325对新型隐球菌的最低抑菌浓度（MIC）分别为2、4和0.25μg/mL，表现出良好的效果。MGB - 353和MGB - 354对结核分枝杆菌的MIC为3.1μM。这些化合物的选择性和活性与其物理化学性质以及感染病原体的细胞壁/膜特性有关。
