Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
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. / Popov, Sergey A.; Semenova, Marya D.; Baev, Dmitry S. и др.
в: Steroids, Том 153, 108524, 01.01.2020.Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
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TY - JOUR
T1 - 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
AU - Popov, Sergey A.
AU - Semenova, Marya D.
AU - Baev, Dmitry S.
AU - Frolova, Tatiana S.
AU - Shults, Elvira E.
AU - Wang, Chengzhang
AU - Turks, Māris
N1 - Publisher Copyright: © 2019 Elsevier Inc.
PY - 2020/1/1
Y1 - 2020/1/1
N2 - 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 amide-linked hydrazides arising from ethoxycarbonylmethyl ursolate and ursolic acid amide with methyl β-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.
AB - 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 amide-linked hydrazides arising from ethoxycarbonylmethyl ursolate and ursolic acid amide with methyl β-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.
KW - 1,2,4-triazole
KW - 1,3,4-oxadiazole
KW - Anti-oxidant
KW - Cytotoxicity tests
KW - Molecular docking
KW - Ursane conjugate
KW - DESIGN
KW - SERIES
KW - TRITERPENOIDS
KW - ANTITUMOR
KW - BIOLOGICAL EVALUATION
KW - INHIBITORS
KW - URSOLIC ACID-DERIVATIVES
UR - http://www.scopus.com/inward/record.url?scp=85073950780&partnerID=8YFLogxK
U2 - 10.1016/j.steroids.2019.108524
DO - 10.1016/j.steroids.2019.108524
M3 - Article
C2 - 31622615
AN - SCOPUS:85073950780
VL - 153
JO - Steroids
JF - Steroids
SN - 0039-128X
M1 - 108524
ER -
ID: 21993113