Antiproliferative Activity, Preliminary QSAR Analysis and in silico ADME Studies of Morita-Baylis-Hillman Adducts from Isatin Derivatives in Four Cancer Cell Lines
Gilmar F. dos Santos, Gardênia Carmen Gadelha Militão, Thiago D. S. Silva, Júlia L. C. Souza, Vinicius B. M. Brito, Eduard David Simões Mourão, Mário L. A. A. Vasconcellos, Edilson Beserra de Alencar Filho, Cláudio Gabriel Lima-Júnior · Revista Virtual de Química · 2022
We present here the antitumor activity of 21 Morita-Baylis-Hillman adducts (MBHA), synthesized by us, followed by structural insights obtained from QSAR and ADME in silico analyses.The activities were determined in four different cancer cell lines, including HL60 (human promyelocytic leukemia), MCF-7 (human breast adenocarcinoma), Hep-2 (cervix carcinoma) and HepG2 (hepatocellular carcinoma).Some of compounds had higher selectivity index (SI) than Doxorubicin.For example, 6 and 9 presented IC 50 of 48 nM and 42 nM against human promyelocytic leukemia, with an SI of 282.10 and 170.00, respectively.Doxorubicin presented IC 50 = 110 nM, with only 12.73 of SI.QSAR procedures provided interesting mathematical models, showing the importance of the nitrile and allyl moieties as well as the possibility of changes in the six-membered ring or isatin nitrogen substituents.SwissADME in silico analysis revealed important discussions about structural requirements for a better pharmacokinetic profile, in future lead optimizations.