Synthesis, molecular modeling and anticancer activities of new molecular hybrids containing 1,4-naphthoquinone, 7-chloroquinoline, 1,3,5-triazine and morpholine cores as PI3K and AMPK inhibitors in the metastatic melanoma cells

Cancer is one of the prominent causes of morbidity and mortality worldwide; it is the second leading cause of death globally, thus, development of new drugs more selective and potent is necessary.1 Molecular Hybridization (MH) is a strategy of rational design of new prototypes, where the lead compound is produced through an adequate fusion of pharmacophoric sub-unities.2 Three molecular hybrids containing 1,4-naphthoquinones, 1,3,5-triazines, morpholine and 7-chloroquinoline, which all have recognized contributions to the biological activity of many drugs, were synthesized in yields ranging from 43%-84%. A previous docking study was carried out to identify the binding energy and pharmacophore conformation of the promising anticancer compounds with PI3Kγ and AMPK. The cancer activity in human metastatic melanoma cells (SKMEL-103) were performed, and the synthetized compounds presented IC¬50¬ values around 25 μM. The expressions of PI3K and AMPK were also determined using western blotting, and all molecular hybrids negatively modulated both targets.