TY - JOUR
T1 - 3-aryl-indolinones derivatives as antiplasmodial agents
T2 - synthesis, biological activity and computational analysis
AU - Luczywo, Ayelen
AU - González, Lucía G.
AU - Aguiar, Anna C.C.
AU - Oliveira de Souza, Juliana
AU - Souza, Guilherme E.
AU - Oliva, Glaucius
AU - Aguilar, Luis F.
AU - Casal, Juan J.
AU - Guido, Rafael V.C.
AU - Asís, Silvia E.
AU - Mellado, Marco
N1 - Publisher Copyright:
© 2021 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - Oxindole derivatives
KW - antimalarial activity
KW - structure-activity relationship
KW - synthesis
UR - http://www.scopus.com/inward/record.url?scp=85102534789&partnerID=8YFLogxK
U2 - 10.1080/14786419.2021.1895149
DO - 10.1080/14786419.2021.1895149
M3 - Article
AN - SCOPUS:85102534789
SN - 1478-6419
VL - 36
SP - 3887
EP - 3893
JO - Natural Product Research
JF - Natural Product Research
IS - 15
ER -