| Author | Oliveira, George Azevedo Reis de | |
| Author | Morales, Bruno Gildo Dalla Vecchia | |
| Author | Sousa, Rosa Maria de Oliveira | |
| Author | Pereira, Soraya dos Santos | |
| Author | Santos, Deborah Antunes dos | |
| Author | Raúl Caffarena, Ernesto | |
| Author | Zanchi, Fernando Berton | |
| Access date | 2024-06-17T13:18:34Z | |
| Available date | 2024-06-17T13:18:34Z | |
| Document date | 2024 | |
| Citation | OLIVEIRA, George Azevedo Reis de et al. Exploring novel antimalarial compounds targeting plasmodium falciparum Enoyl-ACP reductase: computational and experimental insights. ACS Omega, v. 9, n. 21, p. 22777-22793, 13 May 2024. | en_US |
| ISSN | 2470-1343 | en_US |
| URI | https://www.arca.fiocruz.br/handle/icict/64506 | |
| Description | Produção científica do Laboratório de Genômica Aplicada e Bioinovações. | pt_BR |
| Description | Declaration of Generative AI and AI-Assisted Technologies in the Writing Process During the preparation of this work, the authors used ChatGPT in order to enhance the linguistic quality and align the text with academic style. After using this tool/service, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication. | en_US |
| Sponsorship | The Article Processing Charge for the publication of this research was funded by the Coordination for the Improvement of Higher Education Personnel - CAPES (ROR identifier: 00x0ma614). | |
| Sponsorship | The authors would like to thank the National Council of Scientific and Technologic Development (Conselho Nacional de Desenvolvimento Científico e Tecnológico, CNPq), the Rondônia State Foundation of Research Support (Fundação de Amparo àPesquisa do Estado de Rondônia, FAPERO), and the Western Amazon National Institute of Epidemiology (Instituto Nacional de Epidemiologia na Amazônia Ocidental, EPIAMO) for their financial support. This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) - Finance Code 001. | |
| Language | eng | en_US |
| Publisher | American Chemical Society | en_US |
| Rights | open access | |
| Title | Exploring novel antimalarial compounds targeting plasmodium falciparum Enoyl-ACP reductase: computational and experimental insights | en_US |
| Type | Article | |
| DOI | 10.1021/acsomega.3c09893 | |
| Abstract | Malaria, caused by Plasmodium protozoa with Plasmodium falciparum as the most virulent species, continues to pose significant health challenges. Despite the availability of effective antimalarial drugs, the emergence of resistance has heightened the urgency for developing novel therapeutic compounds. In this study, we investigated the enoyl-ACP reductase enzyme of P. falciparum (PfENR) as a promising target for antimalarial drug discovery. Through a comprehensive analysis, we conducted a comparative evaluation of two lead compounds, LD1 (CID: 44405336, lead compounds 1) and LD2 (CID: 72703246, lead compounds 2), obtained from the PubChem/NCBI ligand database, to serve as reference molecules in the identification of potential derivatives using virtual screening assays. Among the newly identified candidates, Ligand 1 (LG1) and Ligand 2 (LG2) exhibited intriguing characteristics and underwent further investigation through docking and molecular dynamics simulations. Ligand 1 (LG1) demonstrated interactions similar to LD1, including hydrogen bonding with Asp218, while Ligand 2 (LG2) displayed superior binding energy comparable to LD1 and LD2, despite lacking hydrogen bonding interactions observed in the control compounds triclosan and its derivative 7-(4-chloro-2-hydroxyphenoxy)-4-methyl-2H-chromen-2-one (CHJ). Following computational validation using the MM/GBSA method to estimate binding free energy, commercially acquired LG1 and LG2 ligands were subjected to in vitro testing. Inhibition assays were performed to evaluate their potential as PfENR inhibitors alongside triclosan as a control compound. LG1 exhibited no inhibitory effects, while LG2 demonstrated inhibitory effects like triclosan. In conclusion, this study contributes valuable insights into developing novel antimalarial drugs by identifying LG2 as a potential ligand and employing a comprehensive approach integrating computational and experimental methodologies. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Fiocruz Rondônia. Laboratório de Bioinformática e Química Medicinal. Porto Velho, RO, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Programa de Pós-Graduação em Biologia Computacional e Sistemas. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Fiocruz Rondônia. Laboratório de Bioinformática e Química Medicinal. Porto Velho, RO, Brasil / Universidade Federal de Rondônia. Programa de Pós-Graduação em Biologia Experimental. Porto Velho, RO, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Fiocruz Rondônia. Laboratório de Engenharia de Anticorpos. Porto Velho, RO, Brasil. | en_US |
| Affilliation | Universidade Federal de Rondônia. Programa de Pós-Graduação em Biologia Experimental. Porto Velho, RO, Brasil / Fundação Oswaldo Cruz. Fiocruz Rondônia. Laboratório de Engenharia de Anticorpos. Porto Velho, RO, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Programa de Pós-Graduação em Biologia Computacional e Sistemas. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genômica Aplicada e Bioinovações. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Coordenação do Programa de Pós-Graduação em Biologia Computacional e Sistemas. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Presidência. Programa de Computação Científica. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Fiocruz Rondônia. Laboratório de Bioinformática e Química Medicinal. Porto Velho, RO, Brasil / Universidade Federal de Rondônia. Porto Velho, RO, Brasil / Fundação Oswaldo Cruz. Fiocruz Rondônia. Instituto Nacional de Epidemiologia na Amazônia Ocidental. Porto Velho, RO, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil. | en_US |
| Subject | Binding energy | en_US |
| Subject | Ligands | en_US |
| Subject | Parasites | en_US |
| Subject | Peptides and proteins | en_US |
| Subject | Screening assays | en_US |
| e-ISSN | 2470-1343 | |
| xmlui.metadata.dc.subject.ods | 07 Energia limpa e acessível | |
