Synthesis and cytotoxicity of hybrids of 1,3,4- or 1,2,5-oxadiazoles tethered from ursane and lupane core with 1,2,3-triazole

Synthesis and cytotoxicity of hybrids of 1,3,4- or 1,2,5-oxadiazoles tethered from ursane and lupane core with 1,2,3-triazole Full article

Journal

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

Output data

Year: 2020, Volume: 162, Article number : 108698, Pages count : DOI: 10.1016/j.steroids.2020.108698

Tags

1,2,3-triazole; 1,3,4- 1,2,5-oxadiazole; 1,3-cycloaddition; Cytotoxicity tests; MDM-2-docking; Triterpenoid conjugate

Authors

Popov S.A. ¹ , Semenova M.D. ¹ , Baev D.S. ¹ , Frolova T.S. ^2,3 , Shestopalov M.A. ⁴ , Wang C. ⁵ , Qi Z. ⁵ , Shults E.E. ¹ , Turks M. ⁶

Affiliations

1	(Scopus) Novosibirsk Institute of Organic Chemistry, Acad. Lavrentyev ave. 9, Novosibirsk, 630090, Russian Federation
2	(Scopus) The Federal Research Center Institute of Cytology and Genetics, Acad. Lavrentyev Ave., 10, Novosibirsk, 630090, Russian Federation
3	(Scopus) Novosibirsk State University, Pirogova Street, 2, Novosibirsk, 630090, Russian Federation
4	(Scopus) Nikolaev Institute of Inorganic Chemistry SB RAS, Acad. Lavrentiev ave., 3, Novosibirsk, 630090, Russian Federation
5	(Scopus) Institute of Chemical Industry of Forest Products, Chinese Academy of Forestry, Nanjing, 210042, China
6	(Scopus) Institute of Technology of Organic Chemistry, Faculty of Materials Science and Applied Chemistry, Riga Technical University, P. Valdena Str. 3, Riga, LV-1048, Latvia

Ursane and lupane type (1-((5-aryl-1,3,4-oxadiazol-2-yl)methyl)-1H-1,2,3-triazol-4-yl)methyl and (1-((4-methyl-2-oxido-1,2,5-oxadiazol-3-yl)methyl)-1H-1,2,3-triazol-4-yl)methyl hybrids were prepared by 1,3-cycloaddition reactions of azole-derived azides with alkyne esters connected to positions C-3 and C-28 of triterpene core and tested for cytotoxicity. Hybrid compounds of 1,3,4-oxadiazoles attached at positions 3- and 28- of triterpenoid frame via triazole spacer and combinations of 1,2,5-oxadiazole or 1,3,4-oxadiazole, tethered with succinate linker and 1,2,3-triazole at the position 3- of the ursane backbone, were inactive in relation to all the cancer cells tested. Eventually, combinations of furoxan fragment and 1,2,3-triazole linked to C-28 position of triterpene backbone demonstrated marked cytotoxic activity towards MCF-7 and HepG2 cells. The most active ester of ursolic acid with (1-((4-methyl-2-oxido-1,2,5-oxadiazol-3-yl)methyl)-1H-1,2,3-triazol-4-yl)methyl substituent and 3-O-acetyl group was superior in activity and selectivity over doxorubicin and ursolic acid on MCF-7 cells. The length of the carbon spacer group may be of crucial importance for cytotoxicity. The introduction of the additional ester linker between the C-28 of triterpenoid and triazole or changing triazole spacer between furoxan moiety and triterpenoid core resulted in activity decrease against all the tested cells. In accordance with molecular modeling results, the activity of new derivatives may be explained in terms of the interaction of the new hybrid molecules and Mdm2 binding sites. © 2020 Elsevier Inc.

Popov S.A. , Semenova M.D. , Baev D.S. , Frolova T.S. , Shestopalov M.A. , Wang C. , Qi Z. , Shults E.E. , Turks M.
Synthesis and cytotoxicity of hybrids of 1,3,4- or 1,2,5-oxadiazoles tethered from ursane and lupane core with 1,2,3-triazole

Steroids. 2020. V.162. 108698 . DOI: 10.1016/j.steroids.2020.108698 WOS Scopus РИНЦ

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Published print:

Oct 1, 2020

Web of science	WOS:000579880800008
Scopus	2-s2.0-85088392393
Elibrary	45420237
OpenAlex	W3043796190