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Malaria Box-Inspired Discovery of N-Aminoalkyl-β-carboline-3-carboxamides, a Novel Orally Active Class of Antimalarials.

ABSTRACT: Virtual ligand screening of a publicly available database of antimalarial hits using a pharmacophore derived from antimalarial MMV008138 identified TCMDC-140230, a tetrahydro-β-carboline amide, as worthy of exploration. All four stereoisomers of this structure were synthesized, but none potently inhibited growth of the malaria parasite Plasmodium falciparum. Interestingly, 7e, a minor byproduct of these syntheses, proved to be potent in vitro against P. falciparum and was orally efficacious (40 mg/kg) in an in vivo mouse model of malaria.

SUBMITTER: Mathew J

PROVIDER: S-EPMC8919280 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Malaria Box-Inspired Discovery of N-Aminoalkyl-β-carboline-3-carboxamides, a Novel Orally Active Class of Antimalarials.

Mathew Jopaul J Ding Sha S Kunz Kevin A KA Stacy Emily E EE Butler Joshua H JH Haney Reagan S RS Merino Emilio F EF Butschek Grant J GJ Rizopoulos Zaira Z Totrov Maxim M Cassera Maria B MB Carlier Paul R PR

ACS medicinal chemistry letters 20220223 3

Virtual ligand screening of a publicly available database of antimalarial hits using a pharmacophore derived from antimalarial MMV008138 identified TCMDC-140230, a tetrahydro-β-carboline amide, as worthy of exploration. All four stereoisomers of this structure were synthesized, but none potently inhibited growth of the malaria parasite Plasmodium falciparum. Interestingly, 7e, a minor byproduct of these syntheses, proved to be potent in vitro against P. falciparum and ...[more]

PMID: 35300096

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