An evaluation of minor groove binders as anti-fungal and anti-mycobacterial therapeutics

Scott, Fraser and Nichol, Ryan J.O. and Khalaf, Abedawn I. and Giordani, Federica and Gillingwater, Kirsten and Ramu, Soumya and Elliott, Alysha and Zuegg, Johannes and Duffy, Paula and Rosslee, Michael-Jon and Hlaka, Lerato and Kumar, Santosh and Ozturk, Mumin and Brombacher, Frank and Barrett, Michael and Guler, Reto and Suckling, Colin J. (2017) An evaluation of minor groove binders as anti-fungal and anti-mycobacterial therapeutics. European Journal of Medicinal Chemistry, 136. pp. 561-572. ISSN 0223-5234

[thumbnail of Scott-etal-EJMC-2017-An-evaluation-of-minor-groove-binders-as-anti-fungal-and-anti-mycobacterial-therapeutics]
Text. Filename: Scott_etal_EJMC_2017_An_evaluation_of_minor_groove_binders_as_anti_fungal_and_anti_mycobacterial_therapeutics.pdf
Accepted Author Manuscript
License: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 logo

Download (1MB)| Preview


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 mg/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.


Scott, Fraser ORCID logoORCID:, Nichol, Ryan J.O., Khalaf, Abedawn I. ORCID logoORCID:, 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 and Suckling, Colin J.;