What question did this study set out to answer?

To optimize N2-acyl tetrahydro-β-carbolines as antimalarial candidates and investigate the structural and stereochemical drivers of their antiparasitic potency.

February 24, 2022ACS Medicinal Chemistry LettersOpen Access

Enantiopure Benzofuran-2-carboxamides of 1-Aryltetrahydro-β-carbolines Are Potent Antimalarials In Vitro

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Authors

HAHanan AlmolhimNorthern Border University SDSha DingVirginia Tech JBJoshua H. ButlerUniversity of Georgia

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Implication

Preclinical study demonstrates potent in vitro activity of novel carbolines against Plasmodium falciparum, indicating poor drug-like properties hinder oral efficacy in mouse models.

Key Points

To optimize N2-acyl tetrahydro-β-carbolines as antimalarial candidates and investigate the structural and stereochemical drivers of their antiparasitic potency.
Conducted similarity searching on public antimalarial databases using MMV008138 to identify hit molecule GNF-Pf-5009 ((±)-3b).
Synthesized pure enantiomers, benzofuran isosteres, and D- and F-ring substitution analogs to evaluate in vitro structure–activity relationships against Plasmodium falciparum.
Tested the lead enantiomer (R)-3b in vivo against Plasmodium berghei-infected mice.
Identified (R)-3b as the pharmacologically superior enantiomer, exhibiting strong in vitro growth inhibition against Plasmodium falciparum.
Established that the benzofuran-2-yl amide moiety is essential for antimalarial activity based on analog synthesis and ring substitutions.
Observed a lack of oral in vivo efficacy for (R)-3b in Plasmodium berghei-infected mice, attributed to unfavorable physicochemical properties.

Cite This Study

Almolhim et al. (2022) studied this question.

synapsesocial.com/papers/6a96fa3f132cd8a75e57a954 https://doi.org/10.1021/acsmedchemlett.1c00697

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Implication

Preclinical study demonstrates potent in vitro activity of novel carbolines against Plasmodium falciparum, indicating poor drug-like properties hinder oral efficacy in mouse models.

Enantiopure Benzofuran-2-carboxamides of 1-Aryltetrahydro-β-carbolines Are Potent Antimalarials In Vitro

Discussion

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Implication

Key Points

Cite This Study

Enantiopure Benzofuran-2-carboxamides of 1-Aryltetrahydro-β-carbolines Are Potent Antimalarials In Vitro

Discussion

Member takes

Implication

Key Points

Cite This Study

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