In silico analysis and molecular docking studies of novel 4-Amino-3-(isoquinolin-4-yl)-1H-pyrazolo[3,4-d]pyrimidine derivatives as Dual PI3K/mTOR inhibitors.

mTORC1/ PI3K control multiple anabolic pathways, including protein synthesis, ribosome production, lipogenesis, and nucleotide synthesis, all of which are important for cell and tissue growth.Sapanisertib and Dactolisib inhibit PI3K/AKT/mTOR pathway, an important signalling pathway for many cellular functions such as growth control, metabolism and translation initiation.Dactolisib contain quinolin-3-yl-2,3-dihydroimidazo[4,5-c]quinolin scaffold and Sapanisertib contain benzo[d]oxazol-5-yl-1-ethyl-1H-pyrazolo[3,4-d]pyrimidinnucleous. From the reference of both of drug novel series of 4-Amino-3-(isoquinolin-4-yl)-1H-pyrazolo[3,4-d]pyrimidin was develop by molecular docking. Among all design derivatives compounds 6( -10.6 kcal/mol) , 12( -10.7 kcal/mol), 14( -10.2 kcal/mol), and 16(-10.2 kcal/mol) have a good binding affinity than others. Biological activity was predicted byMolinspirationonline software tool displays all compounds are active on G- protein coupled receptor. In silico toxicity profile of designed compounds was performed using the SWISSADME programto indicate all the compounds follows the Lipinski rule of five and do not penetrate Blood brain barrier.