An evaluation of Minor Groove Binders as anti-fungal and anti-mycobacterial therapeutics

作者：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

来源：European Journal of Medicinal Chemistry, 2017, 136: 561-572.

DOI：10.1016/j.ejmech.2017.05.039

• Minor Groove Binders
• Anti-infective
• Antifungal
• Anti-tuberculosis

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 MGB5 that are worth more detailed investigation and optimisation. MGB-4, MGB-317 and MGB-325 have promising MIC(80)s of 2, 4 and 0.25 mu g/mL, respectively, against the fungus C neoformans. MGB-353 and MGB-354 have MIC(99)s of 3.1 mu M 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.

• 出版日期2017-8-18