3-aryl-indolinones derivatives as antiplasmodial agents: synthesis, biological activity and computational analysis

• Published in: Natural product research Vol. 36; no. 15; pp. 3887 - 3893
• Main Authors: Luczywo, Ayelen, González, Lucía G., Aguiar, Anna C. C., Oliveira de Souza, Juliana, Souza, Guilherme E., Oliva, Glaucius, Aguilar, Luis F., Casal, Juan J., Guido, Rafael V. C., Asís, Silvia E., Mellado, Marco
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01.08.2022; Taylor & Francis Ltd
• Subjects: antimalarial activity; Antimalarial agents; Antiprotozoal agents; Biological activity; Biological computing; Computer applications; Drug development; L-Lactate dehydrogenase; Lactate dehydrogenase; Lactic acid; Malaria; Molecular docking; Natural products; Oxindole derivatives; structure-activity relationship; synthesis; Vector-borne diseases; synthesis; Oxindole derivatives; antimalarial activity; structure-activity relationship
• ISSN: 1478-6419; 1478-6427
• DOI: 10.1080/14786419.2021.1895149

Malaria is an infectious illness, affecting vulnerable populations in Third World countries. Inspired by natural products, indole alkaloids have been used as a nucleus to design new antimalarial drugs. So, eighteen oxindole derivatives, aza analogues were obtained with moderate to excellent yields. Also, the saturated derivatives of oxindole and aza derivatives via H 2 /Pd/C reduction were obtained in good yields, leading to racemic mixtures of each compound. Next, the inhibitory activity against P. falciparum of 18 compounds were tested, founding six compounds with IC 50 < 20 µM. The most active of these compounds was 8c; however, their unsaturated derivative 7c was inactive. Then, a structure-activity relationship analysis was done, founding that focused LUMO lobe on the specific molecular zone is related to inhibitory activity against P. falciparum. Finally, we found a potential inhibition of lactate dehydrogenase by oxindole derivatives, using molecular docking virtual screening.