Synthesis and Cytotoxicity of Dibenzo[(γ-aryl)pyridino]aza-17-crown-5 Ethers

Le Tuan Anh,^@a Nguyen T. Thanh Phuong,^a Truong Hong Hieu,^b Anatoly T. Soldatenkov,^c Bui T. Van,^a Tran T. Thanh Van,^a Dao T. Nhung,^a Leonid G. Voskressensky,^c To Hai Tung,^aand Victor N. Khrustalev^c,d

^aDepartment of Pharmaceutical Chemistry, Faculty of Chemistry, VNU University of Science, 100000 Hanoi, Vietnam

^bDepartment of Biotechnology, Vietnam-Russia Tropical Centre, 100000 Hanoi, Vietnam

^cFaculty of Science, Peoples’ Friendship University of Russia, 117198 Moscow, Russian Federation

^dX-Ray Structural Centre, A.N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 119991 Moscow, Russian Federation

^@Corresponding author E-mail: huschemical.lab@gmail.com

DOI: 10.6060/mhc170406a

Macroheterocycles 2018 11(2) 197-202

For the development of new anticancer agents, dibenzo[(γ-aryl)pyridino]aza-17-crown-5 ethers containing 2,4,6-triarylpyridine were synthesized successfully by one-step domino-condensation of 1,8-bis(2-acetylphenoxy)-3,6-dioxaoctane, arylaldehydes and ammonium acetate according to the conditions of Hantzsch reactions. The synthesized γ-arylpyridine derivatives show high cytotoxic activity against human cancer cell lines: Hep-G2, RD, FL, Lu1. Compounds (3b,c) showed significant cytotoxicity against all four human cell lines whereas the similar synthesized compound (3d) possessed cytotoxicity against HepG2, Lu1 and RD cell lines. Meantime, both compounds (3f,g) containing γ-heteroaryl only exhibited cytotoxicity against RD and FL cell lines. Azacrown ethers (3b-d) exhibited low activity on the Vero cell line, meaning that they can be evaluated for their potential as promising anticancer agents. X-Ray structure study was performed to determine the structure of the representative compound 3a.

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Synthesis and Cytotoxicity of Dibenzo[(γ-aryl)pyridino]aza-17-crown-5 Ethers

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