Triphenylphosphonium conjugates of 1,2,3-triazolyl nucleoside analogues. Synthesis and cytotoxicity evaluation

Triphenylphosphonium conjugates of 1,2,3-triazolyl nucleoside analogues. Synthesis and cytotoxicity evaluation Full article

Journal

Medicinal Chemistry Research
ISSN: 1554-8120 , E-ISSN: 1054-2523

Output data

Year: 2020, Volume: 29, Number: 12, Pages: 2203-2217 Pages count : 15 DOI: 10.1007/s00044-020-02629-x

Authors

Strobykina Irina Yu. ¹ , Andreeva Olga V. ¹ , Belenok Mayya G. ¹ , Semenova Marina N. ² , Semenov Victor V. ³ , Chuprov-Netochin Roman N. ⁴ , Sapunova Anastasiya S. ¹ , Voloshina Alexandra D. ¹ , Dobrynin Alexey B. ¹ , Semenov Vyacheslav E. ¹ , Kataev Vladimir E. ¹

Affiliations

1	Arbuzov Institute of Organic and Physical Chemistry, Federal Research Center “Kazan Scientific Center of the Russian Academy of Sciences”, Kazan, Russian Federation
2	N. K. Kol’tsov Institute of Developmental Biology, Russian Academy of Sciences, Moscow, Russian Federation
3	N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russian Federation
4	Moscow Institute of Physics and Technology (State University), Moscow Region, Russian Federation

A series of triphenylphosphonium (TPP) conjugates of 1,2,3-triazolyl analogues of several pyrimidine nucleosides was synthesized and evaluated for the in vitro cytotoxicity against human cancer cell lines M-HeLa, MCF-7, PANC-1, PC-3, DU145, SKOV-3, A275, and normal human cell line WI-38. In these TPP-conjugates triphenylphosphonium cation was attached via a tetramethylene chain to the N-3 atom of the heterocycle moiety (uracil, thymine, quinazoline-2,4-dione), which was coupled with the D-ribofuranosyl-1,2,3-triazol-4-yl fragment via methylene or tetramethylene linker. It was shown for the first time that the conjugation of 1,2,3-triazolyl derivatives of uridine, its analogues featuring quinazoline-2,4-dione fragment as well as uracil and thymine derivatives, having propargyl or a 1,2,3-triazolyl substituent at the N-1 atom, with a TPP-butyl cation endowed some of them with cytotoxic activity against human cancer cells. Among all human cancer cell lines used, DU-145 and A375 cells were the most sensitive to these TPP conjugates. At the same time, all tested compounds did not inhibit growth of normal cells WI-38. Propargyl containig TPP-conjugates of uracil 4f, 4j, and thymine 5f showed the highest cytotoxicity with IC50 values in the low micromolar concentration range. The present findings suggest that TPP-conjugates of uracil and thymine derivatives would be promising for further development as an anticancer agent.

Strobykina I.Y. , Andreeva O.V. , Belenok M.G. , Semenova M.N. , Semenov V.V. , Chuprov-Netochin R.N. , Sapunova A.S. , Voloshina A.D. , Dobrynin A.B. , Semenov V.E. , Kataev V.E.
Triphenylphosphonium conjugates of 1,2,3-triazolyl nucleoside analogues. Synthesis and cytotoxicity evaluation
Medicinal Chemistry Research. 2020. V.29. N12. P.2203-2217. DOI: 10.1007/s00044-020-02629-x WOS Scopus OpenAlex

Web of science:	WOS:000573731600001
Scopus:	2-s2.0-85091684290
OpenAlex:	W3091503146

DB	Citing
OpenAlex	12
Scopus	12
Web of science	12