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Structure‐Activity Studies of Truncated Latrunculin Analogues with Antimalarial Activity
Author(s) -
Varghese Swapna,
Rahmani Raphaël,
Drew Damien R.,
Beeson James G.,
Baum Jake,
Smith Brian J.,
Baell Jonathan B.
Publication year - 2021
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.202000399
Subject(s) - motility , biology , drug discovery , plasmodium falciparum , drug , natural product , actin , computational biology , malaria , microbiology and biotechnology , biochemistry , pharmacology , immunology
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.