Abstract
In this study, 7-Acetyl-4-cyano-1,6-dimethyl-6-hydroxy-8- (3-nitrophenyl or 4-nitrophenyl)-5,6,7,8-tetrahydrosoquinoline-3(2H)-thiones 2a-b were synthesized and used as starting materials. Thus, compounds 2a-b were reacted with methyl iodide, ethyl chloroacetate, by heating in ethanol in the presence of sodium acetate trihydrate to give 3-substituted methylthio-5,6,7,8-tetrahydroisoquinoline-4-carbonitriles 3, 4, respectively. In a similar manner, the reaction of compounds 2a-b with N-arylchloroacetamides5a-c afforded the corresponding N-aryl-(5,6,7,8-tetrahydroiso-quinolin-3-ylthio) acetamides 6a-c in excellent yields. In contrast, the reaction of 3b with N-(benzthiazol-2-yl)-2-chloroacetamide (12)under the same (above) conditions yielded 1-amino-N-(benzthiazol-2-yl)-6,7,8,9-tetrahydrothieno[2,3-c]isoquinoline-2-carboxamide13.Cyclization of compounds 6a-c into their 7a-cwas performed by heating in ethanol containing a catalytic amount of sodium ethoxide. 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 andHEGP2 cell lines.The most potent compound against theMCF7 cell lines was compound 9b, and the most potent against HEGP2 cell lines was compound 3. Then the effects of compound 3 on the proliferation of HEPG2 cell lines 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.