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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. et al.

In: Steroids, Vol. 162, 108698, 01.10.2020.

Research output: Contribution to journalArticlepeer-review

Harvard

Popov, SA, Semenova, MD, Baev, DS, Frolova, TS, Shestopalov, MA, Wang, C, Qi, Z, Shults, EE & Turks, M 2020, '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, vol. 162, 108698. https://doi.org/10.1016/j.steroids.2020.108698

APA

Popov, S. A., Semenova, M. D., Baev, D. S., Frolova, T. S., Shestopalov, M. A., Wang, C., Qi, Z., Shults, E. E., & Turks, M. (2020). 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, 162, [108698]. https://doi.org/10.1016/j.steroids.2020.108698

Vancouver

Popov SA, Semenova MD, Baev DS, Frolova TS, Shestopalov MA, Wang C et al. 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 Oct 1;162:108698. Epub 2020 Jul 17. doi: 10.1016/j.steroids.2020.108698

Author

Popov, Sergey A. ; Semenova, Marya D. ; Baev, Dmitry S. et al. / 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. In: Steroids. 2020 ; Vol. 162.

BibTeX

@article{ee877ea556fa4e4dbcef0701096fc500,
title = "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",
abstract = "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.",
keywords = "1,2,3-triazole, 1,3,4- 1,2,5-oxadiazole, 1,3-cycloaddition, Cytotoxicity tests, MDM-2-docking, Triterpenoid conjugate, BETULONIC ACID, SURVIVAL, DESIGN, 1,3,4-1,2,5-oxadiazole, PROLIFERATION, MOLECULES, THERAPY, BETULINIC ACID, PENTACYCLIC TRITERPENOIDS, CLICK-CHEMISTRY, URSOLIC ACID-DERIVATIVES",
author = "Popov, {Sergey A.} and Semenova, {Marya D.} and Baev, {Dmitry S.} and Frolova, {Tatiana S.} and Shestopalov, {Michael A.} and Chengzhang Wang and Zhiwen Qi and Shults, {Elvira E.} and Māris Turks",
note = "Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2020",
month = oct,
day = "1",
doi = "10.1016/j.steroids.2020.108698",
language = "English",
volume = "162",
journal = "Steroids",
issn = "0039-128X",
publisher = "Elsevier Science Inc.",

}

RIS

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