Antiplasmodial activity of sulfonylhydrazones: in vitro and in silico approaches

Malaria is still a life-threatening public health issue, and the upsurge of resistant strains requires continuous generation of active molecules. In this work, 35 sulfonylhydrazone derivatives were synthesized and evaluated against chloroquine-sensitive (3D7) and resistant (W2) strains. The most pro...

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Bibliographic Details
Published in:Future medicinal chemistry 2021-02, Vol.13 (3), p.233-250
Main Authors: Moura Gatti, Fernando de, Gomes, Renan Augusto, da Fonseca, Amanda Luisa, Cardoso Lima, Elys Juliane, Vital-Fujii, Drielli Gomes, Taranto, Alex Guterres, Pilla Varotti, Fernando de, Goulart Trossini, Gustavo Henrique
Format: Article
Language:English
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Summary:Malaria is still a life-threatening public health issue, and the upsurge of resistant strains requires continuous generation of active molecules. In this work, 35 sulfonylhydrazone derivatives were synthesized and evaluated against chloroquine-sensitive (3D7) and resistant (W2) strains. The most promising compound, 5b, had an IC of 0.22 μM against W2 and was less cytotoxic and 26-fold more selective than chloroquine. The structure-activity relationship model, statistical analysis and molecular modeling studies suggested that antiplasmodial activity was related to hydrogen bond acceptor count, molecular weight and partition coefficient of octanol/water and displacement of frontier orbitals to the heteroaromatic ring beside the imine bond. This study demonstrates that the synthesized molecules with a simple scaffold allow the hit-to-lead process for new antimalarials to commence.
ISSN:1756-8919
1756-8927
DOI:10.4155/fmc-2020-0229