Synthesis and evaluation of antitumor, anti-inflammatory and analgesic activity of novel deoxycholic acid derivatives bearing aryl- or hetarylsulfanyl moieties at the C-3 position

Synthesis and evaluation of antitumor, anti-inflammatory and analgesic activity of novel deoxycholic acid derivatives bearing aryl- or hetarylsulfanyl moieties at the C-3 position Full article

Journal

Steroids
ISSN: 0039-128X , E-ISSN: 1878-5867

Output data

Year: 2017, Volume: 127, Pages: 1-12 Pages count : 12 DOI: 10.1016/j.steroids.2017.08.016

Tags

Deoxycholic acid derivatives; Epoxides; Cytotoxicity; Nitric oxide; Anti-inflammatory activity; Antitumor activity

Authors

Popadyuk Irina I. ¹ , Markov Andrey V. ² , Morozova Ekaterina A. ¹ , Babich Valeriya O. ^2,3 , Salomatina Oksana V. ¹ , Logashenko Evgeniya B. ² , Zenkova Marina A. ² , Tolstikova Tat'yana G. ¹ , 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

Novel deoxycholic acid (DCA) derivatives were stereoselectively synthesised with OH and CH2SR moieties at the C-3 position, where R was a substituted aryl [2-aminophenyl (8) or 4-chlorophenyl (9)] or hetaryl [1methylimidazolyl (5), 1,2,4-triazolyl (6), 5-amino-1,3,4-thiadiazolyl (7), pyridinyl (10) or pyrimidinyl (11)]. These compounds were prepared in good yields from the C-313-epoxy derivative 2 in the epoxide ring-opening reaction by S-nucleophiles. These derivatives were evaluated for their its vitro anti-proliferation activity in a panel of tumor cell lines. Data showed that: (i) heterocycle-containing derivatives displayed higher cytotoxicity profiles than the parent molecule; (ii) heterocyclic substituents were more preferable than aryl moieties for enhancing anti-proliferation activity; (iii) the sensitivity of tumor cell lines to analysed compounds decreased in the following order: HuTu-80 (duodenal carcinoma) > KB-3-1 (cervical carcinoma) > HepG2 (hepatocellular carcinoma) > MH-22a (hepatoma); (iv) compounds 5, 6 and 11 exhibited a high cytotoxic selectivity index (HuTu-80: SI > 7.7,38.5 and 12.0, respectively). Compounds 2 and 6-8 markedly inhibited NO synthesis by interferon y-induced macrophages. Screening for anti-inflammatory activity of these derivatives in vivo showed their high potency on histamine-(5, 10) and formalin-(2, 10, 11) induced paw edema models.

Popadyuk I.I. , Markov A.V. , Morozova E.A. , Babich V.O. , Salomatina O.V. , Logashenko E.B. , Zenkova M.A. , Tolstikova T.G. , Salakhutdinov N.F.
Synthesis and evaluation of antitumor, anti-inflammatory and analgesic activity of novel deoxycholic acid derivatives bearing aryl- or hetarylsulfanyl moieties at the C-3 position
Steroids. 2017. V.127. P.1-12. DOI: 10.1016/j.steroids.2017.08.016 WOS Scopus РИНЦ OpenAlex

Published print:

Nov 1, 2017

Web of science:	WOS:000413607900001
Scopus:	2-s2.0-85029130204
Elibrary:	31051667
OpenAlex:	W2750731729

DB	Citing
Web of science	6
Scopus	6
Elibrary	5
OpenAlex	7