文献类型：期刊文献

英文题名：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

作者：Popov, Sergey A.[1] Semenova, Marya D.[1] Baev, Dmitry S.[1] Frolova, Tatiana S.[2,3] Shestopalov, Michael A.[4] Wang, Chengzhang[5] Qi, Zhiwen[5] Shults, Elvira E.[1] Turks, Maris[6]

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]Nikolaev Inst Inorgan Chem SB RAS, Acad Lavrentiev Ave 3, Novosibirsk 630090, Russia;[5]Chinese Acad Forestry, Inst Chem Ind Forest Prod, Nanjing 210042, Peoples R China;[6]Riga Tech Univ, Inst Technol Organ Chem, Fac Mat Sci & Appl Chem, P Valdena Str 3, LV-1048 Riga, Latvia

年份：2020

卷号：162

外文期刊名：STEROIDS

收录：;Scopus(收录号：2-s2.0-85088392393);WOS:【SCI-EXPANDED(收录号:WOS:000579880800008)】；

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

摘要：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.