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

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 ?M) 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.

SUBMITTER: Attram HD

PROVIDER: S-EPMC6457172 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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

Attram Henrietta D HD Wittlin Sergio S Chibale Kelly K

MedChemComm 20190219 3

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 ...[more]

PMID: 31015908

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