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Medchemcomm. 2019 Feb 19;10(3):450-455. doi: 10.1039/c8md00608c. eCollection 2019 Mar 1.

Incorporation of an intramolecular hydrogen bonding motif in the side chain of antimalarial benzimidazoles.

Author information

1
Department of Chemistry , University of Cape Town , Rondebosch 7701 , South Africa . Email: Kelly.Chibale@uct.ac.za ; ; Tel: +27 21 6502553.
2
Swiss Tropical and Public Health Institute , Socinstrasse 57 , 4002 Basel , Switzerland.
3
University of Basel , 4003 Basel , Switzerland.
4
South African Medical Research Council Drug Discovery and Development Research Unit , Department of Chemistry , University of Cape Town , Rondebosch 7701 , South Africa.
5
Institute of Infectious Disease and Molecular Medicine , University of Cape Town , Rondebosch 7701 , South Africa.

Abstract

Analogues of a novel class of benzimidazoles with an intramolecular hydrogen bonding motif have been synthesized and evaluated in vitro for their antiplasmodium activity against chloroquine-sensitive (NF54) and multi-drug resistant (K1) strains of the human malaria parasite Plasmodium falciparum. Compounds were also screened for their cytotoxicity towards a mammalian Chinese hamster ovarian (CHO) cell line. Most of the compounds exhibited good antiplasmodium activity (PfNF54 IC50 <1 μM) and were relatively noncytotoxic. Moreover, towards establishing the possible mode of action of these molecules, inhibition of beta-hematin formation was investigated and two compounds were found to be inhibitors. Single crystal X-ray data confirmed the existence of an intramolecular hydrogen bond.

PMID:
31015908
PMCID:
PMC6457172
[Available on 2020-02-19]
DOI:
10.1039/c8md00608c

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