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Structural Optimization of BIPPO Analogs as Potent Antimalarials

Authors :
Yang Zheng
An Matheeussen
Louis Maes
Guy Caljon
Geert Jan Sterk
Rob Leurs
Source :
Molecules, Vol 28, Iss 13, p 4939 (2023)
Publication Year :
2023
Publisher :
MDPI AG, 2023.

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.

Details

Language :
English
ISSN :
14203049
Volume :
28
Issue :
13
Database :
Directory of Open Access Journals
Journal :
Molecules
Publication Type :
Academic Journal
Accession number :
edsdoj.ffb4457868d42f1a3c374913a0413f2
Document Type :
article
Full Text :
https://doi.org/10.3390/molecules28134939