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

<title>Abstract</title> In this work 7-Acetyl-4-cyano-1, 6-dimethyl-6-hydroxy-8-(2-nitrophenyl)-5,6,7,8-tetrahydrosoquinoline-3(2 <italic>H</italic> )-thione compound <bold>2</bold> was synthesized and used as starting materials. Subsequently, Compounds <bold>3–7</bold> were produced through its reaction with ethyl iodide, ethyl chloroacetate, chloroacetonitrile, and chloroacetaldehyde. Additionally, compound <bold>2</bold> 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 <bold>9a–d</bold> , respectively. Similarly, compounds <bold>2</bold> 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 <bold>9e</bold> . Compounds <bold>9a–e</bold> were cyclized into their <bold>10a</bold> and <bold>d.</bold> Using elemental analysis and spectral data (FT-IR, ¹ H NMR, and ¹³ C 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 <bold>HSF</bold> . Then determine the IC ₅₀ of our drugs against two specific cell lines using various doses. Compound <bold>3</bold> is the most effective chemical against <bold>HEGP2</bold> , according to our research. Compound <bold>9c</bold> was also the most effective compound against <bold>HCT116</bold> . For generally, the tested substances showed moderate anticancer activity, according to the data. The effects of compound <bold>3</bold> on the proliferation of HEGP2 cell lines were then investigated using an apoptotic Annexin V-FITC assay and flow cytometry. Compound <bold>3</bold> increased the HEGP2 cell line's apoptosis by 50 times and caused cell cycle arrest at the G2/M phase.