|
|||||
|
|
Anti-leishmanial evaluation of C2-aryl quinolines: Mechanistic insight on bioenergetics and sterol biosynthetic pathway of Leishmania braziliensis |
|
| Authors: | Daznia Bompart Jorge Núñez-Durán Daniel Rodríguez Vladimir V Kouznetsov Carlos M Meléndez Gómez Felipe Sojo Francisco Arvelo Gonzalo Visbal Alvaro Alvarez Xenón Serrano-Martín Yael García-Marchán |
| Institution: | 1. Laboratorio de Señalización Celular y Bioquímica de Parásitos, Área de Salud, Instituto de Estudios Avanzados (IDEA), Caracas, Bolivarian Republic of Venezuela;2. Laboratorio de Pesquisa Selectiva, Área de Salud, Instituto de Estudios Avanzados (IDEA), Caracas, Bolivarian Republic of Venezuela;3. Área de Salud, Instituto de Estudios Avanzados (IDEA), Caracas, Bolivarian Republic of Venezuela;4. Laboratorio de Química Orgánica y Biomolecular, Universidad Industrial de Santander, Bucaramanga, Colombia;5. Laboratorio de Cultivo de Tejidos y Biología de Tumores, Instituto de Biología Experimental (IBE), Universidad Central de Venezuela, Caracas, Bolivarian Republic of Venezuela;6. Laboratorio de Síntesis Orgánica y Compuestos Naturales, Centro de Química, Instituto Venezolano de Investigaciones Científicas (IVIC), Caracas, Bolivarian Republic of Venezuela |
| Abstract: | A series of diverse simple C2-aryl quinolines was synthesized de novo via a straightforward synthesis based on the acid-catalyzed multicomponent imino Diels–Alder reactions. Seven selected quinolines were evaluated at different stages of Leishmania braziliensis parasite. Among them, the 6-ethyl-2-phenylquinoline 5f was able to inhibit the growth of promastigotes of this parasite without affecting the mammalian cells viability and decreasing the number of intracellular L. braziliensis amastigotes on BMDM macrophages. The mechanism of action studied for the selected compound consisted in: (1) alteration of parasite bioenergetics, by disrupting mitochondrial electrochemical potential and alkalinization of acidocalcisomes, and (2) inhibition of ergosterol biosynthetic pathway in promastigote forms. These results validate the efficiency of quinoline molecules as leishmanicide compounds. |
| Keywords: | Chemotherapy Parasite bioenergetics Sterol biosynthetic pathway C2-aryl substituted quinolines |
| 本文献已被 ScienceDirect 等数据库收录！ | |