Structure-Activity Studies of Truncated Latrunculin Analogues with Antimalarial Activity

Swapna Varghese, Raphaël Rahmani, Damien R. Drew, James G. Beeson, Jake Baum, Brian J. Smith, Jonathan B. Baell

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Malarial parasites employ actin dynamics for motility, and any disruption to these dynamics renders the parasites unable to effectively establish infection. Therefore, actin presents a potential target for malarial drug discovery, and naturally occurring actin inhibitors such as latrunculins are a promising starting point. However, the limited availability of the natural product and the laborious route for synthesis of latrunculins have hindered their potential development as drug candidates. In this regard, we recently described novel truncated latrunculins, with superior actin binding potency and selectivity towards P. falciparum actin than the canonical latrunculin B. In this paper, we further explore the truncated latrunculin core to summarize the SAR for inhibition of malaria motility. This study helps further understand the binding pattern of these analogues in order to develop them as drug candidates for malaria.

Original languageEnglish
Number of pages15
JournalChemMedChem
DOIs
Publication statusPublished - 17 Feb 2021

Keywords

  • Actin inhibitors
  • heterocycles
  • latrunculin analogues
  • malaria
  • natural products
  • P. falciparum

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