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 - Funding Information:
The authors thank to Bioq. M. Belén Iglesias García, Farm. Juan Pablo Carnevale, and to Bioq. Felipe Stambuk for technical assistance. Also, this work was supported by [Universidad de Buenos Aires] under Grant [UBACyT 20020170200206BA]; [Sao Paulo Research Foundation—FAPESP] under Grant [CEPID 2013/07600-3, 18/07287-7, and 17/26679-0]; [National Council for Scientific and Technological Development – CNPq] under Grant [405330/2016-2]; [Instituto Serrapilheira] under Grant [Serra-1708-16250]; [Agencia Nacional de Investigación y Desarrollo (ANID)] under Grant [Fondecyt Postdoctorado 3180408]; and [Pontificia Universidad Católica de Valparaíso] under Grant [VRIEA-PUCV 37.0/2017].
Publisher Copyright:
© 2021 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2021
Y1 - 2021
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
JO - Natural Product Research
JF - Natural Product Research
SN - 1478-6419
ER -