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Structural Optimization of BIPPO Analogs as Potent Antimalarials.

ABSTRACT: Malaria continues to pose a significant health threat, causing thousands of deaths each year. The limited availability of vaccines and medications, combined with the emergence of drug resistance, further complicates the fight against this disease. In this study, we aimed to enhance the antimalarial potency of the previously reported hit compound BIPPO (pIC₅₀ 5.9). Through systematic modification of pyrazolopyrimidinone analogs, we discovered the promising analog 30 (NPD-3547), which exhibited approximately one log unit higher in vitro potency (pIC₅₀ 6.8) against Plasmodium falciparum. Furthermore, we identified several other BIPPO analogs (23, 28, 29 and 47a) with potent antimalarial activity (pIC₅₀ > 6.0) and favorable metabolic stability in mouse liver microsomes. These compounds can serve as new tools for further optimization towards the development of potential candidates for antimalarial studies.

SUBMITTER: Zheng Y

PROVIDER: S-EPMC10343887 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Structural Optimization of BIPPO Analogs as Potent Antimalarials.

Zheng Yang Y Matheeussen An A Maes Louis L Caljon Guy G Sterk Geert Jan GJ Leurs Rob R

Molecules (Basel, Switzerland) 20230623 13

Malaria continues to pose a significant health threat, causing thousands of deaths each year. The limited availability of vaccines and medications, combined with the emergence of drug resistance, further complicates the fight against this disease. In this study, we aimed to enhance the antimalarial potency of the previously reported hit compound BIPPO (pIC50 5.9). Through systematic modification of pyrazolopyrimidinone analogs, we discovered the promising analog 30 (NPD-3547), ...[more]

PMID: 37446602

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