Synthesis of cytotoxic urs-12-ene- and 28-norurs-12-ene- type conjugates with amino- and mercapto-1,3,4-oxadiazoles and mercapto-1,2,4-triazoles

Synthesis of cytotoxic urs-12-ene- and 28-norurs-12-ene- type conjugates with amino- and mercapto-1,3,4-oxadiazoles and mercapto-1,2,4-triazoles Full article

Journal

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

Output data

Year: 2020, Volume: 153, Article number : 108524, Pages count : DOI: 10.1016/j.steroids.2019.108524

Tags

Ursane conjugate; 1,3,4-oxadiazole; 1,2,4-triazole; Anti-oxidant; Cytotoxicity tests; Molecular docking

Authors

Popov Sergey A. ¹ , Semenova Marya D. ¹ , Baev Dmitry S. ^1,3 , Frolova Tatiana S. ^2,3 , Shults Elvira E. ¹ , Wang Chengzhang ⁴ , Turks Maris ⁵

Affiliations

1	(Данные Web of science) Novosibirsk Inst Organ Chem, Acad Lavrentyev Ave 9, Novosibirsk 630090, Russia
2	(Данные Web of science) Fed Res Ctr Inst Cytol & Genet, Acad Lavrentyev Ave 10, Novosibirsk 630090, Russia
3	(Данные Web of science) Novosibirsk State Univ, Pirogova St 2, Novosibirsk 630090, Russia
4	(Данные Web of science) Chinese Acad Forestry, Inst Chem Ind Forest Prod, Nanjing 210042, Peoples R China
5	(Данные Web of science) Riga Tech Univ, Fac Mat Sci & Appl Chem, Inst Technol Organ Chem, P Valdena Str 3, LV-1048 Riga, Latvia

A small library of 2-mercapto-1,3,4-oxadiazoles, 2-amino-1,3,4-oxadiazoles, and 3-mercapto-1,2,4-triazoles attached to the urs-12-ene- and 28-nor-urs-12-ene skeleton has been obtained. Ursolic acid derived hydrazides have been identified as useful starting materials for the developed synthesis. Ursolic acid hydrazide provided access to oxadiazoles attached directly to C-17 of the ursane core, but synthesis of structurally related 3-mercapto-1,2,4-triazoles was not possible in this way due to steric hindrance of the triterpenoid. Ester- and amidelinked hydrazides arising from ethoxycarbonylmethyl ursolate and ursolic acid amide with methyl 13-alaninate served as key starting materials for the remotely connected mercapto-and amino-azoles. Antioxidant activities (DPPH method) of the newly obtained compounds are mediocre. However, excellent cytotoxicity and selectivity against MCF7 cell line were found for 28-nor-urs-12-ene 2-amino-1,3,4-oxadiazole conjugate. Also some other library members exceeded the cytotoxicity values of natural ursolic acid. The novel hybrid heterocycles with amino and mercapto substituents possess a great potential for further derivatization and are prospective scaffolds for the synthesis of triterpenoid analogs with chemopreventive and cytotoxic properties.

Popov S.A. , Semenova M.D. , Baev D.S. , Frolova T.S. , Shults E.E. , Wang C. , Turks M.
Synthesis of cytotoxic urs-12-ene- and 28-norurs-12-ene- type conjugates with amino- and mercapto-1,3,4-oxadiazoles and mercapto-1,2,4-triazoles
Steroids. 2020. V.153. 108524 . DOI: 10.1016/j.steroids.2019.108524 WOS Scopus РИНЦ

Published print:

Jan 1, 2020

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Scopus	2-s2.0-85073950780
Elibrary	41811225
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