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

Ayelen Luczywo, Lucía G. González, Anna C.C. Aguiar, Juliana Oliveira de Souza, Guilherme E. Souza, Glaucius Oliva, Luis F. Aguilar, Juan J. Casal, Rafael V.C. Guido, Silvia E. Asís, MARCO ANDRÉS MELLADO GARCÍA

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
JournalNatural Product Research
DOIs
StateAccepted/In press - 2021
Externally publishedYes

Keywords

  • antimalarial activity
  • Oxindole derivatives
  • structure-activity relationship
  • synthesis

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