| Full text | |
| Author(s): Show less - |
Lima, Marilia N. N.
[1]
;
Neves, Bruno J.
[1, 2]
;
Cassiano, Gustavo C.
[3]
;
Gomes, Marcelo N.
[1, 4, 5]
;
Tomaz, Kaira C. P.
[3]
;
Ferreira, Leticia T.
[3]
;
Tavella, Tatyana A.
[3]
;
Calit, Juliana
[6]
;
Bargieri, Daniel Y.
[6]
;
Muratov, Eugene N.
[7, 8]
;
Costa, Fabio T. M.
[3]
;
Andrade, Carolina Horta
[3, 1]
Total Authors: 12
|
| Affiliation: | [1] Univ Fed Goias, Fac Pharm, Lab Mol Modeling & Drug Design, LabMol, Rua 240, Qd 87, BR-74605170 Goiania, Go - Brazil
[2] Univ Ctr Anapolis UniEVANGEL, Lab Cheminformat, BR-75083515 Anapolis, Go - Brazil
[3] Univ Estadual Campinas, Prof Dr Luiz da Jacintho Silva Dept Genet Evolut, Lab Trop Dis, Inst Biol, BR-13083970 Campinas, SP - Brazil
[4] FAMA, Metropolitan Coll Anapolis, BR-75064780 Anapolis, Go - Brazil
[5] InSiChem Drug Discovery, BR-75132903 Anapolis, Go - Brazil
[6] Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, Sao Paulo, SP - Brazil
[7] Univ N Carolina, Eshelman Sch Pharm, Div Chem Biol & Med Chem, Lab Mol Modeling, Chapel Hill, NC 27955 - USA
[8] Odessa Natl Polytech Univ, Dept Chem Technol, UA-65000 Odessa - Ukraine
Total Affiliations: 8
|
| Document type: | Journal article |
| Source: | Future Medicinal Chemistry; v. 11, n. 20, p. 2635-2646, OCT 2019. |
| Web of Science Citations: | 0 |
| Abstract | |
Aim: Computer-aided drug design approaches were applied to identify chalcones with antiplasmodial activity. Methodology: The virtual screening was performed as follows: structural standardization of in-house database of chalcones; identification of potential Plasmodium falciparum protein targets for the chalcones; homology modeling of the predicted P. falciparum targets; molecular docking studies; and in vitro experimental validation. Results: Using these models, we prioritized 16 chalcones with potential antiplasmodial activity, for further experimental evaluation. Among them, LabMol-86 and LabMol-87 showed potent in vitro antiplasmodial activity against P. falciparum, while LabMol-63 and LabMol-73 were potent inhibitors of Plasodium berghei progression into mosquito stages. Conclusion: Our results encourage the exploration of chalcones in hit-to-lead optimization studies for tackling malaria. {[}GRAPHICS] . (AU) | |
| FAPESP's process: | 17/02031-1 - Evaluation of the antimalarial potential of Epirubicin (4'-epidoxorubicin) |
| Grantee: | Letícia Tiburcio Ferreira |
| Support Opportunities: | Scholarships in Brazil - Master |
| FAPESP's process: | 13/13119-6 - Cell biology and molecular genetics of hemoparasites |
| Grantee: | Daniel Youssef Bargieri |
| Support Opportunities: | Research Grants - Young Investigators Grants |
| FAPESP's process: | 17/02353-9 - Bioinformatics, Chemiogenomics and Chemioinformatics applied to the Discovery of New Drugs and Biotechnological Products |
| Grantee: | Fabio Trindade Maranhão Costa |
| Support Opportunities: | Research Grants - Visiting Researcher Grant - Brazil |
| FAPESP's process: | 17/18611-7 - Development of new tools for search and validation of molecular targets for therapy against Plasmodium vivax |
| Grantee: | Fabio Trindade Maranhão Costa |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 12/16525-2 - Plasmodium vivax: pathogenesis and infectivity |
| Grantee: | Fabio Trindade Maranhão Costa |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 18/24878-9 - Search for Plasmodium transmission-blocking compounds using new experimental models |
| Grantee: | Juliana Calit Paim |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |