Nitrophenyl-Group-Containing Heterocycles. 2. Synthesis, Characterization, Anticancer Activity, Apoptotic Induction and Cell Cycle Arrest of Some New 5,6,7,8-Tetrahydro-isoquinolines Bearing 2-Nitrophenyl Group

Abstract

In this work 7-Acetyl-4-cyano-1, 6-dimethyl-6-hydroxy-8-(2-nitrophenyl)-5,6,7,8-tetrahydrosoquinoline-3(2H)-thione compound 2 was synthesized and used as starting materials. Subsequently, Compounds 3–7 were produced through its reaction with ethyl iodide, ethyl chloroacetate, chloroacetonitrile, and chloroacetaldehyde. Additionally, compound 2 and 2-chloroacetamide were heated in ethanol with sodium acetate trihydrate present, resulting in the formation of 3-Substituted methylthio-5,6,7,8-tetrahydroisoquinoline-4-carbonitriles 9a–d, respectively. Similarly, compounds 2 and N-(1-naphthyl)-2-chloroacetamide reacted to produce high yields of the equivalent N-(1-naphthyl)-(5,6,7,8-tetrahydroiso-quinolin-3-ylthio)acetamides 9e. Compounds 9a–e were cyclized into their 10a and d. Using elemental analysis and spectral data (FT-IR, ¹H NMR, and ¹³C NMR). All newly synthesized compounds were described. The anticancer activity of the produced compounds was also assessed against eight cell lines at one spot concentration and one normal human skin fibroblast cell line HSF. Then determine the IC₅₀ of our drugs against two specific cell lines using various doses. Compound 3 is the most effective chemical against HEGP2, according to our research. Compound 9c was also the most effective compound against HCT116. For generally, the tested substances showed moderate anticancer activity, according to the data. The effects of compound 3 on the proliferation of HEGP2 cell lines were then investigated using an apoptotic Annexin V-FITC assay and flow cytometry. Compound 3 increased the HEGP2 cell line's apoptosis by 50 times and caused cell cycle arrest at the G2/M phase.