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http://hdl.handle.net/1843/72256| Type: | Artigo de Periódico |
| Title: | Revealing the binding process of new 3-alkylpyridine marine alkaloid analogue antimalarials and the heme group: an experimental and theoretical investigation |
| Authors: | Renato Márcio Ribeiro Viana Anna Paola Butera Eliziane da Silva Santos César Augusto Tischer Rosemeire Brondi Alves Rossimiriam Pereira de Freitas Luciana Guimarães Fernando de Pilla Varotti Gustavo Henrique Ribeiro Viana Clebio Soares Nascimento Junior |
| Abstract: | Synthetic 3-alkylpyridine marine alkaloid (3-APA) analogues have shown good antimalarial activity against Plasmodium falciparum. However, despite their structural originality, their molecular target was unknown. Herein, we report a proposal for the antimalarial mechanism of action of 3-APA analogues through interference with the process of hemozoin (Hz) formation. The interaction between 3-APA analogues and heme groups was investigated employing an in silico approach and biophysical techniques such as ultraviolet–visible light (UV-vis) titration and electrospray ionization–mass spectrometry (ESI-MS). The in silico approach was performed based on pure ab initio electronic structure methods in order to obtain insights at the molecular level concerning the binding process of antimalarial drugs at their target site, the heme group. In silico results showed that the formation of heme:3-APA complexes at a molecular ratio of 2:1 are more stable than 1:1 complexes. These results were further confirmed by experimental techniques, such as UV-vis and high-resolution mass spectrometry (ESI-TOF), for two of the most active 3-APA analogues. |
| Subject: | Agentes antiinfecciosos Química bioinorgânica Ligantes (Bioquímica) Alcalóides Plasmodium falciparum Malária Espectrometria de massa |
| language: | eng |
| metadata.dc.publisher.country: | Brasil |
| Publisher: | Universidade Federal de Minas Gerais |
| Publisher Initials: | UFMG |
| metadata.dc.publisher.department: | ICX - DEPARTAMENTO DE QUÍMICA |
| Rights: | Acesso Restrito |
| metadata.dc.identifier.doi: | https://doi.org/10.1021/acs.jcim.5b00742 |
| URI: | http://hdl.handle.net/1843/72256 |
| Issue Date: | 2016 |
| metadata.dc.url.externa: | https://pubs.acs.org/doi/10.1021/acs.jcim.5b00742 |
| metadata.dc.relation.ispartof: | Journal of Chemical Information and Modeling |
| Appears in Collections: | Artigo de Periódico |
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