| Full text | |
| Author(s): |
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
|
| Affiliation: | [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 |
| Abstract | |
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 |