Triphenylphosphonium Cations of the Diterpenoid Isosteviol: Synthesis and Antimitotic Activity in a Sea Urchin Embryo Model

Triphenylphosphonium Cations of the Diterpenoid Isosteviol: Synthesis and Antimitotic Activity in a Sea Urchin Embryo Model Full article

Journal

Journal of Natural Products
ISSN: 0163-3864 , E-ISSN: 1520-6025

Output data

Year: 2015, Volume: 78, Number: 6, Pages: 1300-1308 Pages count : 9 DOI: 10.1021/acs.jnatprod.5b00124

Authors

Strobykina Irina Yu ¹ , Belenok Mayya G ¹ , Semenova Marina N ^2,3 , Semenov Victor V ⁴ , Babaev Vasiliy M ¹ , Rizvanov Ildar Kh ¹ , Mironov Vladimir F ¹ , Kataev Vladimir E ¹

Affiliations

1	†A. E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Center of Russian Academy of Sciences, Arbuzov Street, 8, 420088, Kazan, Russian Federation.
2	Chemical Block Ltd., 3 Kyriacou Matsi, 3723 Limassol, Cyprus
3	N. K. Kol’tsov Institute of Developmental Biology, Russian Academy of Sciences, Vavilov Street, 26, 119334, Moscow, Russian Federation
4	N. D. Zelinsky Institute of Organic Chemistry , Russian Academy of Sciences , Leninsky prospect 47 , 119991 Moscow , Russian Federation.

A series of novel triphenylphosphonium (TPP) cations of the diterpenoid isosteviol (1, 16-oxo-ent-beyeran-19-oic acid) have been synthesized and evaluated in an in vivo phenotypic sea urchin embryo assay for antimitotic activity. The TPP moiety was applied as a carrier to provide selective accumulation of a connected compound into mitochondria. When applied to fertilized eggs, the targeted isosteviol TPP conjugates induced mitotic arrest with the formation of aberrant multipolar mitotic spindles, whereas both isosteviol and the methyltriphenylphosphonium cation were inactive. The structure–activity relationship study revealed the essential role of the TPP group for the realization of the isosteviol effect, while the chemical structure and the length of the linker only slightly influenced the antimitotic potency. The results obtained using the sea urchin embryo model suggested that TPP conjugates of isosteviol induced mitotic spindle defects and mitotic arrest presumably by affecting mitochondrial DNA. Since targeting mitochondria is considered as an encouraging strategy for cancer therapy, TPP-isosteviol conjugates may represent promising candidates for further design as anticancer agents.

Strobykina I.Y. , Belenok M.G. , Semenova M.N. , Semenov V.V. , Babaev V.M. , Rizvanov I.K. , Mironov V.F. , Kataev V.E.
Triphenylphosphonium Cations of the Diterpenoid Isosteviol: Synthesis and Antimitotic Activity in a Sea Urchin Embryo Model
Journal of Natural Products. 2015. V.78. N6. P.1300-1308. DOI: 10.1021/acs.jnatprod.5b00124 WOS Scopus OpenAlex

Web of science:	WOS:000357138300015
Scopus:	2-s2.0-84933059832
OpenAlex:	W627238693

DB	Citing
OpenAlex	59
Scopus	57
Web of science	56