New Polyether Macrocycles as Promising Antitumor Agents─Targeted Synthesis and Induction of Mitochondrial Apoptosis

New Polyether Macrocycles as Promising Antitumor Agents─Targeted Synthesis and Induction of Mitochondrial Apoptosis Full article

Journal

ACS Omega
ISSN: 2470-1343

Output data

Year: 2024, Volume: 9, Number: 18, Pages: 19923-19931 Pages count : 9 DOI: 10.1021/acsomega.3c09566

Authors

Islamov Ilgiz I. ¹ , Dzhemileva Lilya U. ^2,3 , Gaisin Ilgam V. ¹ , Dzhemilev Usein M. ² , D′yakonov Vladimir A. ²

Affiliations

1	Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, 141 Prospekt Oktyabrya, Ufa 450075, Russian Federation
2	N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospekt, 47, Moscow 119991, Russian Federation
3	State Scientific Center of the Russian Federation Federal State Budgetary Institution, "National Medical Research Center of Endocrinology" of the Ministry of Health of the Russian Federation, st. Dmitry Ulyanov, 11, Moscow 117292, Russian Federation

A series of previously unknown aromatic polyether macrodiolides containing a cis,cis-1,5-diene moiety in the molecule were synthesized in 47–74% yields. Macrocycle compounds were first obtained by intermolecular esterification of aromatic polyether diols with α,ω-alka-nZ,(n+4)Z-dienedioic acids mediated by N-(3-(dimethylamino)propyl)-N′-ethylcarbodiimide hydrochloride (EDC·HCl) and 4-(dimethylamino)pyridine (DMAP). For the synthesized compounds, studies of cytotoxicity on tumor (Jurkat, K562, U937), conditionally normal (HEK293) cell lines, and normal fibroblasts were carried out. CC50 was determined, and the therapeutic selectivity index of cytotoxic action (SI) in comparison with normal fibroblasts was evaluated. With the involvement of modern methods of flow cytometry for the most promising macrocycles, their effect on mitochondria and the cell cycle was investigated. It was found that a new macrocycle exhibits pronounced apoptosis-inducing activity toward Jurkat cells and can retard cell division by blocking at the G1/S checkpoint. Also, it was shown that the synthesized macrodiolides influence mitochondria due to their high ability to penetrate the mitochondrial membrane.

Islamov I.I. , Dzhemileva L.U. , Gaisin I.V. , Dzhemilev U.M. , D′yakonov V.A.
New Polyether Macrocycles as Promising Antitumor Agents─Targeted Synthesis and Induction of Mitochondrial Apoptosis
ACS Omega. 2024. V.9. N18. P.19923-19931. DOI: 10.1021/acsomega.3c09566 WOS Scopus OpenAlex

Web of science:	WOS:001227728800001
Scopus:	2-s2.0-85192217549
OpenAlex:	W4396222869

DB	Citing
OpenAlex	6
Scopus	4
Web of science	4