2. Academic Validation
  3. 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

  • J Nat Prod. 2015 Jun 26;78(6):1300-8. doi: 10.1021/acs.jnatprod.5b00124.
Irina Yu Strobykina 1,  Mayya G Belenok 1,  Marina N Semenova 2 3,  Victor V Semenov 4,  Vasiliy M Babaev 1,  Ildar Kh Rizvanov 1,  Vladimir F Mironov 1,  Vladimir E Kataev 1
Affiliations

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 ‡N. K. Kol'tsov Institute of Developmental Biology, Russian Academy of Sciences, Vavilov Street, 26, 119334, Moscow, Russian Federation.
  • 3 §Chemical Block Ltd., 3 Kyriacou Matsi, 3723 Limassol, Cyprus.
  • 4 ⊥N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect, 47, 119991, Moscow, Russian Federation.
PMID: 26042548 DOI: 10.1021/acs.jnatprod.5b00124
Abstract

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.

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