Synthesis and in vitro antitumor activity of novel alkenyl derivatives of pyridoxine, bioisosteric analogs of feruloyl methane.

Autor: Pavelyev RS; Kazan (Volga region) Federal University, Kremlyovskaya 18, 420008 Kazan, Russia., Bondar OV; Kazan (Volga region) Federal University, Kremlyovskaya 18, 420008 Kazan, Russia., Nguyen TNT; Kazan (Volga region) Federal University, Kremlyovskaya 18, 420008 Kazan, Russia., Ziganshina AA; Kazan (Volga region) Federal University, Kremlyovskaya 18, 420008 Kazan, Russia., Al Farroukh M; Kazan (Volga region) Federal University, Kremlyovskaya 18, 420008 Kazan, Russia., Karwt R; Kazan (Volga region) Federal University, Kremlyovskaya 18, 420008 Kazan, Russia., Alekbaeva GD; Kazan (Volga region) Federal University, Kremlyovskaya 18, 420008 Kazan, Russia., Pugachev MV; Kazan (Volga region) Federal University, Kremlyovskaya 18, 420008 Kazan, Russia., Yamaleeva ZR; A.E. Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, Arbuzov Str. 8, Kazan 420088, Russia., Kataeva ON; A.E. Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, Arbuzov Str. 8, Kazan 420088, Russia., Balakin KV; Kazan (Volga region) Federal University, Kremlyovskaya 18, 420008 Kazan, Russia; I.M. Sechenov First Moscow State Medical University, Trubetskaya 8, Bldg. 2, 119991 Moscow, Russia., Shtyrlin YG; Kazan (Volga region) Federal University, Kremlyovskaya 18, 420008 Kazan, Russia. Electronic address: yurii.shtyrlin@gmail.com.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry [Bioorg Med Chem] 2018 Dec 01; Vol. 26 (22), pp. 5824-5837. Date of Electronic Publication: 2018 Oct 27.
DOI: 10.1016/j.bmc.2018.10.031
Abstrakt: Two series of novel pyridoxine-based azaheterocyclic analogs of feruloyl methane (Dehydrozingerone, DZG) were synthesized, and their biological activity against a panel of tumor and normal cell lines was evaluated in vitro. The most active compounds possessed expressed cytotoxic activity, which was comparable to cytotoxic activity of doxorubicin and significantly higher than that of DZG, and a remarkable selectivity for the studied cancer cell lines as compared to the normal cells. The leading compound and DZG initiated arrest of the cell cycle in the G2/M phase, preventing normal division and further transition of daughter cells to the G0/G1 phase. Similar to DZG, but with higher efficiency, the leading compound was able to inhibit migration activity and, therefore, invasiveness of tumor cells. It also increased concentration of reactive oxygen species in tumor cells, induced depolarization of mitochondrial membranes and initiated apoptosis accompanied by disruption of integrity of cytoplasmic cell membranes. By contrast to DZG, the leading compound did not possess antioxidant properties. The obtained data make the described chemotype a promising starting point for the development of new anticancer agents.
(Copyright © 2018 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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