Synthesis and cytotoxicity of novel simplified eleutherobin analogues as potential antitumour agents

Synthesis and cytotoxicity of novel simplified eleutherobin analogues as potential antitumour agents Full article

Journal

Organic & Biomolecular Chemistry
ISSN: 1477-0520 , E-ISSN: 1477-0539

Output data

Year: 2019, Volume: 17, Number: 10, Pages: 2792-2797 Pages count : 6 DOI: 10.1039/c8ob02915f

Authors

Sosonyuk Sergey E. ¹ , Peshich Anita ¹ , Tutushkina Anastasia V. ¹ , Khlevin Dmitry A. ¹ , Lozinskaya Natalia A. ^1,2 , Gracheva Yulia A. ¹ , Glazunova Valeria A. ³ , Osolodkin Dmitry I. ^1,5,4 , Semenova Marina N. ⁶ , Semenov Victor V. ⁷ , Palyulin Vladimir A. ^1,2 , Proskurnina Marina V. ^1,2 , Shtil Alexander A. ^1,3 , Zefirov Nikolay S. ^1,2

Affiliations

1	Department of Chemistry, Lomonosov Moscow State University, 1-3 Leninskie Gory, Moscow, Russia
2	Institute of Physiologically Active Compounds, Russian Academy of Sciences, 1 Severniy Proezd, Chernogolovka, Moscow Region, Russia
3	Blokhin National Medical Center of Oncology, 24 Kashirskoye Shosse, Moscow, Russia
4	FSBSI “Chumakov FSC R&D IBP RAS”, 8 bd. 1 Poselok Instituta Poliomielita, Poselenie Moskovsky, Moscow 108819, Russia
5	Institute of Translational Medicine and Biotechnology, Sechenov First Moscow State Medical University, Moscow 119991, Russia
6	Institute of Developmental Biology, Russian Academy of Sciences, Moscow, Russia
7	Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia

Mixed simplified structures containing the paclitaxel and eleutherobin pharmacophore moieties were analyzed using molecular docking techniques and synthesized based on adamantane and 8-oxabicyclo[3.2.1]octane scaffolds. The crucial role of substituents’ stereochemistry in biological activity is discussed. At micromolar concentrations the selected analogues interfered with tubulin dynamics in vitro and in a living organism. Furthermore, new compounds were cytotoxic against human tumour cell lines. The simplified eleutherobin analogues may be considered as prototypes of a new class of antitumour agents.

Sosonyuk S.E. , Peshich A. , Tutushkina A.V. , Khlevin D.A. , Lozinskaya N.A. , Gracheva Y.A. , Glazunova V.A. , Osolodkin D.I. , Semenova M.N. , Semenov V.V. , Palyulin V.A. , Proskurnina M.V. , Shtil A.A. , Zefirov N.S.
Synthesis and cytotoxicity of novel simplified eleutherobin analogues as potential antitumour agents
Organic & Biomolecular Chemistry. 2019. V.17. N10. P.2792-2797. DOI: 10.1039/c8ob02915f WOS Scopus OpenAlex

Web of science:	WOS:000460594400025
Scopus:	2-s2.0-85062447682
OpenAlex:	W2913855301

DB	Citing
OpenAlex	11
Scopus	11
Web of science	10