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

Fraser Scott, Ryan J.O. Nichol, Abedawn I. Khalaf, Federica Giordani, Kirsten Gillingwater, Soumya Ramu, Alysha Elliott, Johannes Zuegg, Paula Duffy, Michael-Jon Rosslee, Lerato Hlaka, Santosh Kumar, Mumin Ozturk, Frank Brombacher, Michael Barrett, Reto Guler, Colin J. Suckling

Research output: Contribution to journalArticle

6 Citations (Scopus)
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Abstract

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.
Original languageEnglish
Pages (from-to)561-572
Number of pages12
JournalEuropean Journal of Medicinal Chemistry
Volume136
Early online date17 May 2017
Publication statusPublished - 18 Aug 2017

Keywords

  • minor Groove Binders
  • anti-infective
  • antifungal
  • anti-tuberculosis
  • resistance
  • drug-resistant
  • Cryptococcus neoformans
  • Mycobacterium tuberculosis

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