Title

Discovery of highly selective 7-chloroquinolinethiohydantoins with potent antimalarial activity

ORCID

Kirkwood M. Land: 0000-0001-5951-9630

Document Type

Article

Publication Title

European Journal of Medicinal Chemistry

Department

Biological Sciences

ISSN

0223-5234

Volume

84

DOI

10.1016/j.ejmech.2014.07.048

First Page

425

Last Page

432

Publication Date

9-12-2014

Abstract

A series of C-3 thiourea functionalized β-lactams, β-lactam-7-chloroquinoline conjugates and 7-chloroquinoline-thiohydantoin derivatives were prepared with the aim of probing antimalarial structure–activity relationships. 7-Chlorquinoline-thiohydantoin derivatives were found to be potent inhibitors of cultured Plasmodium falciparum, with the most potent and non-cytotoxic compound exhibiting an IC50 of 39.8 nM. Studies of β-hematin formation suggested that inhibition of haemozoin formation could be primary mechanism of action, with IC50 values comparable to those of chloroquine. Evaluation of cytotoxicity against HeLa cells demonstrated high selective indices.

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