Nitrophenyl-group-containing Heterocycles. 3. New Isoquinolines, as antiprolifative agents against MCF7and  HEGP2  Cell  lines. Synthesis, characterization and biological Evaluation.

In this study, new tetrahydrosoquinoline compounds were synthesized by reacted with methyl iodide, chloro acetonitrile, ethyl chloroacetate, N-arylchloroacetamides N-and (benzthiazol-2-yl)-2-chloroacetamide reagents to gave tetrahydroiso-quinolin-3-ylthio) acetamides ( 5a-c ) which can cyclized to tetrahydroiso-quinolin-3-ylthio) acetamides ( 6a-c) in excellent yields. The structures of all newly synthesized compounds were characterized by elemental and spectral analyses. Also, most of the synthesized compounds were evaluated for their anticancer activity in MCF7 and HEPG2 cell lines. From the result we found that the most potent compound against the MCF7 cell lines was compound 9b , and the most active against HEPG2 cell lines was compound 3. Then the effects of compound 3 on the HEPG2 cell line was investigated using an apoptotic Annexin V-FITC test and flow cytometry. Compound 3 induced a 59-fold increase in HEPG2 cell line apoptosis and cell cycle arrested at the G0-G1, G2/M phases. Moreover, the molecular docking study was applied and the result showed that compounds 9b bind to the RET enzyme with binding energies of -6.8 kcal/mol in comparison with standard alectinib , which exhibits a binding energy of -7.2 kcal/mol. Compound 3 can bind with HSP 90 with a binding energy (ΔG) of -6.8 kcal/mol, which is comparable to the standard Onalespib (-7.1 kcal/mol).