Antiplasmodial activity of sulfonylhydrazones: in vitro and in silico approaches
| Autor: | Gustavo Henrique Goulart Trossini, Renan Augusto Gomes, Elys Juliane Cardoso Lima, Drielli Gomes Vital-Fujii, Amanda Luisa da Fonseca, Fernando de Pilla Varotti, Alex Guterres Taranto, Fernando de Moura Gatti |
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| Rok vydání: | 2021 |
| Předmět: |
Pharmacology
0303 health sciences biology 010405 organic chemistry In silico Plasmodium falciparum Computational biology medicine.disease biology.organism_classification 01 natural sciences In vitro 0104 chemical sciences 03 medical and health sciences Drug Discovery medicine Molecular Medicine Malaria 030304 developmental biology |
| Zdroj: | Future Medicinal Chemistry. 13:233-250 |
| ISSN: | 1756-8927 1756-8919 |
| Popis: | 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 Plasmodium falciparum chloroquine-sensitive (3D7) and resistant (W2) strains. The most promising compound, 5b, had an IC50 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. |
| Databáze: | OpenAIRE |
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