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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Antiplasmodial activity of sulfonylhydrazones: in vitro and in silico approaches

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Moura Gatti, Fernando de [1] ; Gomes, Renan Augusto [1] ; da Fonseca, Amanda Luisa [2] ; Cardoso Lima, Elys Juliane [1] ; Vital-Fujii, Drielli Gomes [1] ; Taranto, Alex Guterres [2] ; Pilla Varotti, Fernando de [2] ; Goulart Trossini, Gustavo Henrique [1]
Total Authors: 8
[1] Univ Sao Paulo, Fac Ciencias Farmaceuti, Av Prof Lineu Prestes 580, BR-05508000 Sao Paulo, SP - Brazil
[2] Inst Biociencias, BR-36307352 Sao Joao Del Rei, MG - Brazil
Total Affiliations: 2
Document type: Journal article
Source: Future Medicinal Chemistry; v. 13, n. 3, p. 233-250, FEB 2021.
Web of Science Citations: 0

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 mu M 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. (AU)

FAPESP's process: 13/15650-0 - Application of Structure-Based Drug Design in parasite cysteine protease inhibitor search (cruzain (T. cruzi and CPB (Leishmanioses))
Grantee:Drielli Gomes Vital Fujii
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 17/25543-8 - Medicinal Chemistry strategies (LBDD and SBDD) in the search of tripanomatides sirtuin 2 inhibitors
Grantee:Gustavo Henrique Goulart Trossini
Support Opportunities: Regular Research Grants