| Texto completo | |
| Autor(es): |
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]
Número total de Autores: 8
|
| Afiliação do(s) autor(es): | [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
Número total de Afiliações: 2
|
| Tipo de documento: | Artigo Científico |
| Fonte: | Future Medicinal Chemistry; v. 13, n. 3, p. 233-250, FEB 2021. |
| Citações Web of Science: | 0 |
| Resumo | |
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) | |
| Processo FAPESP: | 13/15650-0 - APLICAÇÃO DE PLANEJAMENTO BASEADO NA ESTRUTURA DO RECEPTOR NA BUSCA DE INIBIDORES DE CISTEÍNO- PROTEASES PARASITÁRIAS (CRUZAÍNA (T. cruzi) e CPB (Leishmanioses)) |
| Beneficiário: | Drielli Gomes Vital Fujii |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado |
| Processo FAPESP: | 17/25543-8 - Estratégias de Química Medicinal (LBDD e SBDD) na busca de inibidores de Sirtuína 2 de tripanossomatídeos |
| Beneficiário: | Gustavo Henrique Goulart Trossini |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |