- 3-aryl-indolinones derivatives as antiplasmodial agents: synthesis, biological activity and computational analysis
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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.
- 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
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supporting information
(2021/03/18)
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- Pd(0)-Catalyzed Chemoselective Deacylative Alkylations (DaA) of N-Acyl 2-Oxindoles: Total Syntheses of Pyrrolidino[2,3- b]indoline Alkaloids, (±)-Deoxyeseroline, and (±)-Esermethole
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We report an efficient Pd(0)-catalyzed deacylative allylation of N-acyl 3-substituted 2-oxindoles via the coupling of in situ generated nucleophiles (3 and 4) with allyl electrophiles for the synthesis of a variety of 2-oxindoles with C3-quaternary centers. Gratifyingly, this alkylation process is found to be highly chemoselective in nature, where a C-C bond formation is completely predominant over a C-N bond formation. A variety of key intermediates were synthesized utilizing an aforementioned methodology.
- Kumar, Nivesh,Gavit, Vipin R.,Maity, Arindam,Bisai, Alakesh
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p. 10709 - 10735
(2018/09/29)
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