Cytotoxic conjugates of betulinic acid and substituted triazoles prepared by Huisgen Cycloaddition from 30-azidoderivatives

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F17%3A73583737" target="_blank" >RIV/61989592:15110/17:73583737 - isvavai.cz</a>

Alternative codes found

RIV/61989592:15310/17:73583737

Result on the web

<a href="http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0171621" target="_blank" >http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0171621</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1371/journal.pone.0171621" target="_blank" >10.1371/journal.pone.0171621</a>

Result language

angličtina

Original language name

Cytotoxic conjugates of betulinic acid and substituted triazoles prepared by Huisgen Cycloaddition from 30-azidoderivatives

Original language description

In this work, we describe synthesis of conjugates of betulinic acid with substituted triazoles prepared via Huisgen 1,3-cycloaddition. All compounds contain free 28-COOH group. Allylic bromination of protected betulinic acid by NBS gave corresponding 30-bromoderivatives, their substitution with sodium azides produced 30-azidoderivatives and these azides were subjected to CuI catalysed Huisgen 1,3-cycloaddition to give the final conjugates. Reactions had moderate to high yields. All new compounds were tested for their in vitro cytotoxic activities on eight cancer and two non-cancer cell lines. The most active compounds were conjugates of 3β-O-acetylbetulinic acid and among them, conjugate with triazole substituted by benzaldehyde 9b was the best with IC50 of 3.3 µM and therapeutic index of 9.1. Five compounds in this study had IC50 below 10 µM and inhibited DNA and RNA synthesis and caused block in G0/G1 cell cycle phase which is highly similar to actinomycin D. It is unusual that here prepared 3β-O-acetates were more active than compounds with the free 3-OH group and this suggests that this set may have common mechanism of action that is different from the mechanism of action of previously known 3β-O-acetoxybetulinic acid derivatives. Benzaldehyde type conjugate 9b is the best candidate for further drug development.

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

PLoS One

ISSN

1932-6203

e-ISSN

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Volume of the periodical

12

Issue of the periodical within the volume

2

Country of publishing house

US - UNITED STATES

Number of pages

25

Pages from-to

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UT code for WoS article

000396161700114

EID of the result in the Scopus database

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