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

AGUIAR, ANNA C. C.; OLIVA, GLAUCIUS; GUIDO, RAFAEL V. C.; GONZÁLEZ, LUCÍA G.; SOUZA, GUILHERME E.; CASAL, JUAN J.; MELLADO, MARCO; LUCZYWO, AYELEN; OLIVEIRA DE SOUZA, JULIANA; AGUILAR, LUIS F.; ASÍS, SILVIA E.

NATURAL PRODUCT RESEARCH

TAYLOR & FRANCIS LTD

Año: 2021 vol. 36 p. 3887 - 3893

1478-6419

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 H2/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 IC50 < 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.