Design, Synthesis, and Evaluation of Alkoxyamine Anticancer Prodrugs Bearing Galactoside as an Enzyme-Activated Trigger

Design, Synthesis, and Evaluation of Alkoxyamine Anticancer Prodrugs Bearing Galactoside as an Enzyme-Activated Trigger Full article

Journal

Chemical Research in Toxicology
ISSN: 1520-5010 , E-ISSN: 0893-228X

Output data

Year: 2026, Volume: 39, Number: 8, Pages: 1584-1594 Pages count : 11 DOI: 10.1021/acs.chemrestox.6c00193

Authors

Kolesnikova Yuliana A. ¹ , Abramov Alexander A. ¹ , Eskova Daria D. ¹ , Votkina Darya E. ¹ , Plotnikov Evgenii V. ¹ , Tretyakov Evgeny V. ² , Marque Sylvain R.A. ³ , Audran Gérard ³ , Postnikov Pavel S. ^4,1 , Stepanova Elena V. ¹ , Petunin Pavel V. ¹

Affiliations

1	Tomsk Polytechnic University , , 30 Lenin Av. , ,
2	Russian Academy of Sciences , , 47 Leninsky Av. , ,
3	Aix Marseille University , , Case 551, Avenue Escadrille Normandie-Niemen , ,
4	Siberian Branch of the Russian Academy of Sciences , , Lavrentiev Av. 9 , ,

Enzyme-induced cytotoxicity can be considered the main challenge in modern cancer therapy that provides unique opportunities for targeted apoptosis. To address this challenge, we implemented enzyme-triggered activation of alkoxyamine–galactose conjugates with the formation of active carbon-centered radical species for the apoptosis of cancer cells. The comparative analysis of two alkoxyamine derivatives, bearing stable and self-immolative linkers between the radical precursor and galactose moiety, revealed the crucial role of molecular structure in anticancer activity. The study of cytotoxicity and induced oxidative stress of free amine and two galactosides revealed the enzyme-dependent nature of the activity of alkoxyamines having a self-immolative linker against distinct cancer cell lines such as PC-3 (prostate adenocarcinoma), SKOV-3 (ovarian adenocarcinoma), MCF-7 (breast adenocarcinoma), A-431 (epidermoid carcinoma), and Jurkat cells (human T-lymphoblastic leukemia). The collected data prove the applicability of enzyme-triggered glycosylated alkoxyamines as a new family of targeted prodrugs against cancer.

Kolesnikova Y.A. , Abramov A.A. , Eskova D.D. , Votkina D.E. , Plotnikov E.V. , Tretyakov E.V. , Marque S.R.A. , Audran G. , Postnikov P.S. , Stepanova E.V. , Petunin P.V.
Design, Synthesis, and Evaluation of Alkoxyamine Anticancer Prodrugs Bearing Galactoside as an Enzyme-Activated Trigger
Chemical Research in Toxicology. 2026. V.39. N8. P.1584-1594. DOI: 10.1021/acs.chemrestox.6c00193 WOS Scopus OpenAlex

Submitted:	Mar 29, 2026
Accepted:	Jul 17, 2026
Published print:	Aug 4, 2026
Published online:	Aug 17, 2026

≡ Web of science:	WOS:001841430300001
≡ Scopus:	2-s2.0-105047546512
≡ OpenAlex:	W7172418266