Nitrophenyl-Group-Containing Heterocycles. I. Synthesis, Characterization, Crystal Structure, Anticancer Activity, and Antioxidant Properties of Some New 5,6,7,8-Tetrahydroisoquinolines Bearing 3(4)-Nitrophenyl Group

• DOI: 10.1021/acsomega.1c06994
• Publication Date: 2022-03-04T10:49:49Z
• Authors: Eman M. Sayed; Reda Hassanien; Nasser Farhan; Hanan F. Aly; Khaled Mahmoud; Shaaban K. Mohamed; Joel T. Mague; Etify A. Bakhite
• Keywords: Tetrahydroisoquinoline; Isoquinoline; Cancer cell lines

Regioselective cyclocondensation of 2,4-diacetyl-5-hydroxy-5-methyl-3-(3-nitrophenyl/4-nitrophenyl)cyclohexanones 1a,b with cyanothioacetamide afforded the corresponding 7-acetyl-4-cyano-1,6-dimethyl-6-hydroxy-8-(3- and -4-nitrophenyl)-5,6,7,8-tetrahydrosoquinoline-3(2H)-thiones 2a,b. Reaction compounds 2a,b ethyl iodide, 2-chloroacetamide (4a), or its N-aryl derivatives 4b-e in presence sodium acetate trihydrate gave 3-ethylthio-5,6,7,8-tetrahydroisoquinoline 3 (5,6,7,8-tetrahydroisoquinolin-3-ylthio)acetamides 5a-i, respectively. Cyclization 5b-d,f,g into their isomeric 1-amino-6,7,8,9-tetrahydrothieno[2,3-c]isoquinoline-2-carboxamides 6b-d,f,g was achieved by heating ethanol containing a catalytic amount carbonate. Structures all synthesized were characterized on basis elemental analyses spectroscopic data. The crystal structure 5,6,7,8-tetrahydroisoquinoline 5d determined X-ray diffraction analysis. In addition, biological evaluation some as anticancer agents performed, only six showed moderate to strong activity against PACA2 (pancreatic cancer cell line) A549 (lung carcinoma line). Moreover, antioxidant properties most examined. results revealed high for tested compounds.