Research Articles

2017  |  Vol: 3(3)  |  Issue: 3(May-June)
Chemical Modification of Tetrahydroisoquinolines and their Cytotoxic Activity

Еkaterina О. Тerentevaa*Zaynat SKhashimovab, Еlena АTsayaSherzod NZhurakulova, Аbdusalom ShSaidovcValentina IVinogradovaaShakhnoz SAzimovaa

aInstitute of the Chemistry of Plant Substances, Uzbek Academy of Sciences, M. Ulugbek str. 77, 100170 Tashkent, Uzbekistan; 

bInstitute of the Bioorganic Chemistry, Uzbek Academy of Sciences, M. Ulugbek str. 83, 100125 Tashkent, Uzbekistan; 

cSamarkand State University, Str. University Boulevard, 15, 140104 Samarkand, Uzbekistan.

*Corresponding author

Еkaterina О. Тerenteva

Institute of the Chemistry of Plant Substances, Uzbek Academy of Sciences, M. Ulugbek str. 77, 100170 Tashkent, Uzbekistan

 

Abstract

Objective: The wide variety of potent biological activities of natural and synthetic isoquinoline alkaloids encouraged us to develop novel cytotoxic isoquinoline compounds. A variety of differently functionalized 1-aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolines were synthesized. Materials and methods: We employed classic intramolecular Bischler-Napieralski cyclodehydration to generate the isoquinoline core. All the structures were characterized by nuclear magnetic resonance and mass spectrometry. The cytotoxic activities against three human cancer cell lines and primary culture of healthy hepatocyte cells were evaluated for all the synthesized compounds and structure-activity relationships were established by MTT asay. Results: It was shown that 8a has demonstrated selective cytotoxicity against breast adenocarcinoma (IC50: 43.3 µM), 4d, 3f against laryngeal adenocarcinoma (IC50: 18.0 and 2.3 µM respectively) with the absence of toxicity to healthy cells. Bis compounds exhibit greater cytotoxic effect than mono-series compounds. Among bis samples 8f showed the greatest cytotoxic properties with an IC50 value of 3.1-4.0 µM. The all conjugate compounds completely lacked cytotoxicity toward cancer cell lines in this study. 10 b,d demonstrated proliferative activity. Conclusions: Thus, the most promising compounds for further study in vitro and in vivo methods are dibasic compound 8d, 8e. Later these substances can be offered as a basis for drugs with anti-tumor properties.

Keywords: 1,2,3,4-tetrahydroisoquinoline derivatives, Bischler-Napieralski cyclization, cancer cells, cytotoxicity


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