Novel Tetraene Macrodiolides Are Effective Inducers of Mitochondrial Apoptosis in Jurkat Cells

Novel Tetraene Macrodiolides Are Effective Inducers of Mitochondrial Apoptosis in Jurkat Cells Full article

Journal

International Journal of Molecular Sciences
ISSN: 1661-6596 , E-ISSN: 1422-0067

Output data

Year: 2025, Volume: 26, Number: 11, Article number : 5139, Pages count : DOI: 10.3390/ijms26115139

Authors

Islamov Ilgiz I. ¹ , Dzhemileva Lilya U. ² , Gaisin Ilgam V. ¹ , Makarov Alexey A. ¹ , Dzhemilev Usein M. ² , D’yakonov Vladimir A. ²

Affiliations

1	Institute of Petrochemistry and Catalysis, Ufa Federal Research Centre, Russian Academy of Sciences, 141 Prospekt Oktyabrya, Ufa 450075, Russia
2	N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect 47, Moscow 119991, Russia

We synthesized 16 representatives of a new class of tetraene macrodiolides with two pharmacophore cis,cis-1,5-diene fragments of the molecule in their structure in rather high yields (from 67 to 84%), which, in turn, were synthesized by a catalytic intermolecular cyclocondensation reaction of α,ω-alka-nZ,(n+4)Z-diendiols with α,ω-alka-nZ,(n+4)Z-diendioic acids using Hf(OTf)4. The synthesis of starting substrates with 1Z,5Z-diene moieties with a high degree of stereoselectivity was carried out using the authors’ original reaction of catalytic homo-cyclomagnesiation of O-containing allenes. The cytotoxic potential of the examined compounds was assessed using the following cell lines: Jurkat, K562, U937, HL60, HEK293, and Wi-38 (fibroblasts). Biological tests of the synthesized compounds showed a direct effect on mitochondrial biogenesis by the dissociation of oxidation and phosphorylation and the release of cytochrome P450 into the cell cytosol, as well as the induction of mitochondrial apoptosis. The selectivity index demonstrates significant variability, ranging from approximately 2.5 to 5.3 for Jurkat cells and from 3.0 to 5.8 for the other cell lines.

Islamov I.I. , Dzhemileva L.U. , Gaisin I.V. , Makarov A.A. , Dzhemilev U.M. , D’yakonov V.A.
Novel Tetraene Macrodiolides Are Effective Inducers of Mitochondrial Apoptosis in Jurkat Cells
International Journal of Molecular Sciences. 2025. V.26. N11. 5139 . DOI: 10.3390/ijms26115139 WOS Scopus OpenAlex

Web of science:	WOS:001505979500001
Scopus:	2-s2.0-105007675086
OpenAlex:	W4410833231

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