An evaluation of Minor Groove Binders as anti-fungal and anti-mycobacterial therapeutics.
Scott FJ, Nichol RJO, Khalaf AI, Giordani F, Gillingwater K, Ramu S, Elliott A, Zuegg J, Duffy P, Rosslee MJ, Hlaka L, Kumar S, Ozturk M, Brombacher F, Barrett M, Guler R, Suckling CJ.
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 MIC80s of 2, 4 and 0.25 μg/mL, respectively, against the fungus C. neoformans.MGB-353 and MGB-354 have MIC99s 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.