Design and synthesis of pentacyclic triterpene conjugates and their use in medicinal research

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F19%3A73597047" target="_blank" >RIV/61989592:15110/19:73597047 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15310/19:73597047

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0223523419307937" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0223523419307937</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ejmech.2019.111653" target="_blank" >10.1016/j.ejmech.2019.111653</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Design and synthesis of pentacyclic triterpene conjugates and their use in medicinal research

Popis výsledku v původním jazyce

Triterpenoids are natural products from plants and many other organisms that have various biological activities, such as antitumor, antiviral, antimicrobial, and protective activities. This review covers the synthesis and biological evaluation of pentacyclic triterpene (PT) conjugates with other molecules that have been found to increase the IC50 or improve the pharmacological profile of the parent PT. Some of these molecules are designed to target specific proteins or cellular organelles, which has resulted in highly selective lead structures for drug development. Other PT conjugates are useful for investigating their mechanism of action. This concept has been very successful: 1) Many compounds, especially mitochondria-targeting PT conjugates, have reached a selective cytotoxicity at low nanomolar concentrations in cancer cells. 2) A number of PT conjugates have had high activity against HIV or the influenza virus. 3) Fluorescent PT conjugates have been able to visualize the FT in living cells, which has allowed quantification of the uptake and distribution of the PT within the cell. 4) Biotinylated PT conjugates have been used to identify target proteins, which may help to show their mechanism of action. 5) A large number of PT conjugates with polyethylene glycol (PEG), polyamines, etc. form nanometer-sized micelles that have a much better pharmacological profile than the PT alone. In summary, the connection of a PT to an appropriate modifying molecule has resulted in extremely useful semisynthetic compounds with a high potential to treat cancer or viral infections or compounds that are useful for the study of the mechanism of action of PTs at the molecular level. (C) 2019 Elsevier Masson SAS. All rights reserved.

Název v anglickém jazyce

Design and synthesis of pentacyclic triterpene conjugates and their use in medicinal research

Popis výsledku anglicky

Triterpenoids are natural products from plants and many other organisms that have various biological activities, such as antitumor, antiviral, antimicrobial, and protective activities. This review covers the synthesis and biological evaluation of pentacyclic triterpene (PT) conjugates with other molecules that have been found to increase the IC50 or improve the pharmacological profile of the parent PT. Some of these molecules are designed to target specific proteins or cellular organelles, which has resulted in highly selective lead structures for drug development. Other PT conjugates are useful for investigating their mechanism of action. This concept has been very successful: 1) Many compounds, especially mitochondria-targeting PT conjugates, have reached a selective cytotoxicity at low nanomolar concentrations in cancer cells. 2) A number of PT conjugates have had high activity against HIV or the influenza virus. 3) Fluorescent PT conjugates have been able to visualize the FT in living cells, which has allowed quantification of the uptake and distribution of the PT within the cell. 4) Biotinylated PT conjugates have been used to identify target proteins, which may help to show their mechanism of action. 5) A large number of PT conjugates with polyethylene glycol (PEG), polyamines, etc. form nanometer-sized micelles that have a much better pharmacological profile than the PT alone. In summary, the connection of a PT to an appropriate modifying molecule has resulted in extremely useful semisynthetic compounds with a high potential to treat cancer or viral infections or compounds that are useful for the study of the mechanism of action of PTs at the molecular level. (C) 2019 Elsevier Masson SAS. All rights reserved.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10401 - Organic chemistry

Projekt

<a href="/cs/project/EF16_019%2F0000868" target="_blank" >EF16_019/0000868: Molekulární, buněčný a klinický přístup ke zdravému stárnutí</a><br>

Návaznosti

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

Rok uplatnění

2019

Kód důvěrnosti údajů

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

Název periodika

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

ISSN

0223-5234

e-ISSN

—

Svazek periodika

182

Číslo periodika v rámci svazku

NOV

Stát vydavatele periodika

FR - Francouzská republika

Počet stran výsledku

25

Strana od-do

"111653-1"-"111653-25"

Kód UT WoS článku

000496896600012

EID výsledku v databázi Scopus

2-s2.0-85071770857