文献类型：期刊文献

英文题名：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

作者：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]

第一作者：Popov, Sergey A.

通信作者：Popov, SA[1]

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

年份：2020

卷号：153

外文期刊名：STEROIDS

收录：;Scopus(收录号：2-s2.0-85073950780);WOS:【SCI-EXPANDED(收录号:WOS:000509615100009)】；

基金：This research was financially supported by the ERA.Net RUS Plus project #RUS_ST2017-139 "AnticancerBet" (Foundation of Basic Research Grant 18-53-76001)). Immortalized human fibroblasts were kindly provided by A. Schilov (Institute of Cytology and Genetics of Siberian Branch of Russian Academy of Sciences, Novosibirsk, Russia). Analytical and spectroscopic studies were performed at the Chemical Service collective Center of SB RAS.

语种：英文

外文关键词：Ursane conjugate; 1,3,4-oxadiazole; 1,2,4-triazole; Anti-oxidant; Cytotoxicity tests; Molecular docking

摘要：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.