Synthesis and Cytotoxic Activity of Triterpenoid Thiazoles Derived from Allobetulin, Methyl Betulonate, Methyl Oleanonate, and Oleanonic Acid

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F17%3A73583551" target="_blank" >RIV/61989592:15110/17:73583551 - isvavai.cz</a>

Alternative codes found

RIV/61989592:15310/17:73583551 RIV/60461373:22330/17:43913137

Result on the web

<a href="http://dx.doi.org/10.1002/cmdc.201600626" target="_blank" >http://dx.doi.org/10.1002/cmdc.201600626</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/cmdc.201600626" target="_blank" >10.1002/cmdc.201600626</a>

Result language

angličtina

Original language name

Synthesis and Cytotoxic Activity of Triterpenoid Thiazoles Derived from Allobetulin, Methyl Betulonate, Methyl Oleanonate, and Oleanonic Acid

Original language description

A total of 41 new triterpenoids were prepared from allobetulone, methyl betulonate, methyl oleanonate, and oleanonic acid to study their influence on cancer cells. Each 3-oxotriterpene was brominated at C2 and substituted with thiocyanate; subsequent cyclization with the appropriate ammonium salts gave N-substituted thiazoles. All compounds were tested for their in vitro cytotoxic activity on eight cancer cell lines and two non-cancer fibroblasts. 2-Bromoallobetulone (2b) methyl 2-bromobetulonate (3b), 2-bromooleanonic acid (5b), and 2-thiocyanooleanonic acid (5c) were best, with IC50 values less than 10 mm against CCRF-CEM cells (e.g., 3b: IC50=2.9 mm) as well as 2’-(diethylamino)olean-12(13)-eno[2,3-d]thiazole-28-oic acid (5 f, IC50=9.7 mm) and 2’-(N-methylpiperazino)olean- 12(13)-eno[2,3-d]thiazole-28-oic acid (5k, IC50=11.4 mm). Compound 5c leads to the accumulation of cells in the G2 phase of the cell cycle and inhibits RNA and DNA synthesis significantly at 1VIC50. The G2/M cell-cycle arrest probably corresponds to the inhibition of DNA/RNA synthesis, similar to the mechanism of action of actinomycin D. Compound 5c is new, active, and nontoxic; it is therefore the most promising compound in this series for future drug development. Methyl 2-bromobetulonate (3b) and methyl 2-thiocyanometulonate (3c) were found to inhibit nucleic acid synthesis only at 5VIC50. We assume that in 3b and 3c (unlike in 5c), DNA/RNA inhibition is a nonspecific event, and an unknown primary cytotoxic target is activated at 1VIC50 or lower concentration.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10401 - Organic chemistry

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2017

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

ChemMedChem

ISSN

1860-7179

e-ISSN

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Volume of the periodical

2017

Issue of the periodical within the volume

12

Country of publishing house

DE - GERMANY

Number of pages

9

Pages from-to

390-398

UT code for WoS article

000395629900008

EID of the result in the Scopus database

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