Síntese, modelagem molecular e avaliação da atividade fotossintética de derivados 1,4-dihidropiridinas

• Ano de defesa: 2022
• Autor(a) principal: Soares, Luís Teylon Xavier Machado Gulart
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Mato Grosso; Brasil; Instituto de Ciências Exatas e da Terra (ICET); UFMT CUC - Cuiabá; Programa de Pós-Graduação em Química
• Palavras-chave em Português: Dihidropiridinas; Docking molecular; Fluorescência da clorofila a; Fotossistema II; CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA; Dihydropyridines; Molecular docking; Chlorophyll a fluorescence; Photosystem II
• Link de acesso: http://ri.ufmt.br/handle/1/7458

With the need of the agricultural sector to combat weeds, chemical control is necessary in order to obtain better quality and production yield. Due to the fact that many agricultural pesticides bring negative impacts to human health and the environment, studies for the development of new bioactive compounds are essential, especially for countries that have their economy focused on agribusiness. Given the scenario presented, this work carried out the synthesis of derivatives of 1,4-dihydropyridines (1,4-DHP) using the multicomponent Hantzsch reaction, followed by the investigation of the herbicidal activity of these compounds. Through the chlorophyll a fluorescence assay, the potential to inhibit the flow of electrons in photosystem II (PSII) was evaluated. Among the synthesized compounds, 1,1'- (2,4,6-trimethyl-1,4-dihydropyridine-3,5-diyl)bis(ethan-1-one) presented the best result, by reducing the performance index parameters on the basis of electron absorption and electron transport per reaction center by 61% and 49%, respectively, compared to the control. This result demonstrates the inhibitory activity of 1,4-DHPs on the PSII electron transport chain. To investigate the structure-activity relationship of synthetic compounds on PSII, molecular docking was performed using the D1 protein (PDB code 4V82), which showed a relationship between the volume of the substituent group at position 4 of the DHP ring and the activity performed, with the bulky groups were responsible for decreasing the inhibitory potential. 1,4-DHPs can exert D1 blocking activity through hydrogen bonding interactions, carried out mainly between the carbonyls and the amino acid residues His215, and Phe265, in addition to the interaction between Ser264 and the NH group. DHPs show great potential as molecular scaffolds for the development of PSII inhibitor molecules, and the structural optimization of compounds can be explored.