Amides of moronic acid and morolic acid with the tripeptides MAG and GAM targeting antimicrobial, antiviral and cytotoxic effects

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389030%3A_____%2F25%3A00616545" target="_blank" >RIV/61389030:_____/25:00616545 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61388963:_____/25:00616545 RIV/61989592:15310/25:73628012 RIV/60461373:22330/25:43931019

Výsledek na webu

<a href="https://doi.org/10.1039/d4md00742e" target="_blank" >https://doi.org/10.1039/d4md00742e</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1039/d4md00742e" target="_blank" >10.1039/d4md00742e</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Amides of moronic acid and morolic acid with the tripeptides MAG and GAM targeting antimicrobial, antiviral and cytotoxic effects

Popis výsledku v původním jazyce

A series of amides of selected plant triterpenoids, moronic acid and morolic acid, with the tripeptides MAG and GAM, was designed and synthesized. Two required tripeptides 5 and 10 were synthesized by a step-wise chain elongation of the ethyl esters of either glycine or L-methionine at their N-terminus using Boc-protected amino acids in each step. The tripeptides 5 and 10 were used for the synthesis of 13-23, the derivatives of moronic acid (11) and morolic acid (12), to get a series of amide derivatives of the less frequently studied triterpenoids 11 and 12. The target compounds, and their intermediates, were subjected to an investigation of their antimicrobial, antiviral and cytotoxic activity. Selectivity of the pharmacological effects was found. Generally, the target compounds inhibited only the G(+) microorganisms. Compound 16 inhibited Staphylococcus aureus (I = 99.6%, c = 62.5 mu M) and Enterococcus faecalis (I = 85%, c = 250 mu M). Several compounds showed moderate antiviral effects, both anti-HIV-1, 19 (EC50 = 57.0 +/- 4.1 mu M, CC50 > 100 mu M), 20 (EC50 = 17.8 +/- 2.1 mu M, CC50 = 41.0 +/- 5.2 mu M) and 23 (EC50 = 12.6 +/- 0.82 mu M, CC50 = 38.0 +/- 4.2 mu M), and anti-HSV-1, 22 (EC50 = 27.7 +/- 3.5 mu M, CC50 > 100 mu M) and 23 (EC50 = 30.9 +/- 3.3 mu M, CC50 > 100 mu M). The target compounds showed no cytotoxicity in cancer cells, however, several of their intermediates were cytotoxic. Compound 21 showed cytotoxicity in HeLa (IC50 = 7.9 +/- 2.1 mu M), G-361 (IC50 = 8.0 +/- 0.6 mu M) and MCF7 (IC50 = 8.6 +/- 0.2 mu M) cancer cell lines, while being non-toxic in normal fibroblasts (BJ, IC50 > 50 mu M).

Název v anglickém jazyce

Amides of moronic acid and morolic acid with the tripeptides MAG and GAM targeting antimicrobial, antiviral and cytotoxic effects

Popis výsledku anglicky

A series of amides of selected plant triterpenoids, moronic acid and morolic acid, with the tripeptides MAG and GAM, was designed and synthesized. Two required tripeptides 5 and 10 were synthesized by a step-wise chain elongation of the ethyl esters of either glycine or L-methionine at their N-terminus using Boc-protected amino acids in each step. The tripeptides 5 and 10 were used for the synthesis of 13-23, the derivatives of moronic acid (11) and morolic acid (12), to get a series of amide derivatives of the less frequently studied triterpenoids 11 and 12. The target compounds, and their intermediates, were subjected to an investigation of their antimicrobial, antiviral and cytotoxic activity. Selectivity of the pharmacological effects was found. Generally, the target compounds inhibited only the G(+) microorganisms. Compound 16 inhibited Staphylococcus aureus (I = 99.6%, c = 62.5 mu M) and Enterococcus faecalis (I = 85%, c = 250 mu M). Several compounds showed moderate antiviral effects, both anti-HIV-1, 19 (EC50 = 57.0 +/- 4.1 mu M, CC50 > 100 mu M), 20 (EC50 = 17.8 +/- 2.1 mu M, CC50 = 41.0 +/- 5.2 mu M) and 23 (EC50 = 12.6 +/- 0.82 mu M, CC50 = 38.0 +/- 4.2 mu M), and anti-HSV-1, 22 (EC50 = 27.7 +/- 3.5 mu M, CC50 > 100 mu M) and 23 (EC50 = 30.9 +/- 3.3 mu M, CC50 > 100 mu M). The target compounds showed no cytotoxicity in cancer cells, however, several of their intermediates were cytotoxic. Compound 21 showed cytotoxicity in HeLa (IC50 = 7.9 +/- 2.1 mu M), G-361 (IC50 = 8.0 +/- 0.6 mu M) and MCF7 (IC50 = 8.6 +/- 0.2 mu M) cancer cell lines, while being non-toxic in normal fibroblasts (BJ, IC50 > 50 mu M).

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10401 - Organic chemistry

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

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

Název periodika

RSC Medicinal Chemistry

ISSN

2632-8682

e-ISSN

2632-8682

Svazek periodika

16

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

11

Strana od-do

801-811

Kód UT WoS článku

001353773700001

EID výsledku v databázi Scopus

2-s2.0-85208810916