Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
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. / Popov, Sergey A.; Semenova, Marya D.; Baev, Dmitry S. и др.
в: Steroids, Том 162, 108698, 01.10.2020.Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
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TY - JOUR
T1 - 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
AU - Popov, Sergey A.
AU - Semenova, Marya D.
AU - Baev, Dmitry S.
AU - Frolova, Tatiana S.
AU - Shestopalov, Michael A.
AU - Wang, Chengzhang
AU - Qi, Zhiwen
AU - Shults, Elvira E.
AU - Turks, Māris
N1 - Publisher Copyright: © 2020 Elsevier Inc.
PY - 2020/10/1
Y1 - 2020/10/1
N2 - 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.
AB - 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.
KW - 1,2,3-triazole
KW - 1,3,4- 1,2,5-oxadiazole
KW - 1,3-cycloaddition
KW - Cytotoxicity tests
KW - MDM-2-docking
KW - Triterpenoid conjugate
KW - BETULONIC ACID
KW - SURVIVAL
KW - DESIGN
KW - 1,3,4-1,2,5-oxadiazole
KW - PROLIFERATION
KW - MOLECULES
KW - THERAPY
KW - BETULINIC ACID
KW - PENTACYCLIC TRITERPENOIDS
KW - CLICK-CHEMISTRY
KW - URSOLIC ACID-DERIVATIVES
UR - http://www.scopus.com/inward/record.url?scp=85088392393&partnerID=8YFLogxK
U2 - 10.1016/j.steroids.2020.108698
DO - 10.1016/j.steroids.2020.108698
M3 - Article
C2 - 32687846
AN - SCOPUS:85088392393
VL - 162
JO - Steroids
JF - Steroids
SN - 0039-128X
M1 - 108698
ER -
ID: 24832887