Novel derivatives of deoxycholic acid bearing aliphatic or cyclic diamine moieties at the C-3 position: Synthesis and evaluation of anti-proliferative activity

Novel derivatives of deoxycholic acid bearing aliphatic or cyclic diamine moieties at the C-3 position: Synthesis and evaluation of anti-proliferative activity Full article

Journal

Bioorganic and Medicinal Chemistry Letters
ISSN: 0960-894X , E-ISSN: 1464-3405

Output data

Year: 2017, Volume: 27, Number: 16, Pages: 3755-3759 Pages count : 5 DOI: 10.1016/j.bmcl.2017.06.072

Tags

Deoxycholic acid derivatives; Epoxides; Diamines; Cytotoxicity; Anti-proliferative activity

Authors

Popadyuk Irina I. ¹ , Markov Andrey V. ² , Babich Valeriya O. ^2,3 , Salomatina Oksana V. ¹ , Logashenko Evgeniya B. ² , Zenkova Marina A. ² , Salakhutdinov Nariman F. ^1,3

Affiliations

1	(Данные Web of science) Russian Acad Sci, Siberian Branch, NN Vorozhtsov Novosibirsk Inst Organ Chem, 9 Lavrentev Ave, Novosibirsk 630090, Russia
2	(Данные Web of science) Russian Acad Sci, Siberian Branch, Inst Chem Biol & Fundamental Med, 8 Lavrentev Ave, Novosibirsk 630090, Russia
3	(Данные Web of science) Novosibirsk State Univ, 2 Pirogova Str, Novosibirsk 630090, Russia

A new library of deoxycholic acid derivatives bearing nitrogen-containing moieties at the C-3 position was synthesised from epoxy derivative 1 via an epoxide ring-opening reaction promoted by aliphatic or cyclic diamines and fully characterised by NMR and mass-spectroscopy. The synthesised compounds were screened for cytotoxicity against four human tumour cell lines. The results showed that some of the novel diamine-bearing derivatives displayed improved anti-proliferative activities over the parent compound DCA. Among them, a 1-methylpiperazine containing compound (6) showed promising activity and the highest selectivity against tumour cells of enterohepatic origin (HepG2: IC50 = 3.6 mu M, SI = 9.0; HuTu-80: IC50 = 4.6 mu M, SI = 6.9) and was identified as a lead molecule. (C) 2017 Elsevier Ltd. All rights reserved.

Popadyuk I.I. , Markov A.V. , Babich V.O. , Salomatina O.V. , Logashenko E.B. , Zenkova M.A. , Salakhutdinov N.F.
Novel derivatives of deoxycholic acid bearing aliphatic or cyclic diamine moieties at the C-3 position: Synthesis and evaluation of anti-proliferative activity
Bioorganic and Medicinal Chemistry Letters. 2017. V.27. N16. P.3755-3759. DOI: 10.1016/j.bmcl.2017.06.072 WOS Scopus РИНЦ

Published print:

Aug 1, 2017

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