Premium
A Structure–Activity Relationship Study of the Antimalarial and Antileishmanial Activities of Nonpeptide Macrocyclic Histone Deacetylase Inhibitors
Author(s) -
Guerrant William,
Mwakwari Sandra C.,
Chen Po C.,
Khan Shabana I.,
Tekwani Babu L.,
Oyelere Adegboyega K.
Publication year - 2010
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.201000087
Subject(s) - histone deacetylase , antiparasitic agent , antiparasitic , biology , computational biology , stereochemistry , histone deacetylase inhibitor , virtual screening , identification (biology) , histone , chemistry , biochemistry , pharmacology , drug discovery , medicine , pathology , gene , botany
Histone deacetylase inhibitors (HDACi) cause a diverse range of responses in biological systems. The depth of the antiparasitic capabilities of macrocyclic HDACi was determined against malarial and leishmanial pathogens. Antiparasitic activities of macrocyclic HDACi derived from macrolide skeletons are dependent on the length ( n ) of the spacer group that separates their zinc‐binding and surface‐recognition moieties. Antimalarial activities peak when n =6, whereas antileishmanial activities are optimum when n =8–9. This observation could facilitate the identification of other HDACi that are more selective for either parasite.