In vitro biological evaluation of new antimycobacterial salicylanilide-tuftsin conjugates

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F17%3A10364360" target="_blank" >RIV/00216208:11160/17:10364360 - isvavai.cz</a>

Alternative codes found

RIV/71009396:_____/17:N0000003

Result on the web

<a href="http://www.sciencedirect.com/science/article/pii/S0223523417302039" target="_blank" >http://www.sciencedirect.com/science/article/pii/S0223523417302039</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ejmech.2017.03.047" target="_blank" >10.1016/j.ejmech.2017.03.047</a>

Result language

angličtina

Original language name

In vitro biological evaluation of new antimycobacterial salicylanilide-tuftsin conjugates

Original language description

Tuberculosis is caused by Mycobacterium tuberculosis, an intracellular pathogen that can survive in host cells, mainly in macrophages. An increase of multidrug-resistant tuberculosis qualifies this infectious disease as a major public health problem worldwide. The cellular uptake of the antimycobacterial agents by infected host cells is limited. Our approach is to enhance the cellular uptake of the antituberculars by target cell-directed delivery using drug-peptide conjugates to achieve an increased intracellular efficacy. In this study, salicylanilide derivatives (2-hydroxy-N-phenylbenzamides) with remarkable antimycobacterial activity were conjugated to macrophage receptor specific tuftsin based peptide carriers through oxime bond directly or by insertion of a GFLG tetrapeptide spacer. We have found that the in vitro antimycobacterial activity of the salicylanilides against M. tuberculosis H(37)Rv is preserved in the conjugates. While the free drug was ineffective on infected macrophage model, the conjugates were active against the intracellular bacteria. The fluorescently labelled peptide carriers that were modified with different fatty acid side chains showed outstanding cellular uptake rate to the macrophage model cells. The conjugation of the salicylanilides to tuftsin based carriers reduced or abolished the in vitro cytostatic activity of the free drugs with the exception of the palmitoylated conjugates. The conjugates degraded in the presence of rat liver lysosomal homogenate leading to the formation of an oxime bond linked salicylanilide-amino acid fragment as the smallest active metabolite. (C) 2017 Published by Elsevier Masson SAS.

Czech name

—

Czech description

—

Type

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

CEP classification

—

OECD FORD branch

30104 - Pharmacology and pharmacy

Project

<a href="/en/project/GJ17-27514Y" target="_blank" >GJ17-27514Y: Peptide Drug Delivery Systems Targeting Macrophages for Antimycobacterial Active Compounds</a><br>

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

European Journal of Medicinal Chemistry

ISSN

0223-5234

e-ISSN

—

Volume of the periodical

133

Issue of the periodical within the volume

June

Country of publishing house

FR - FRANCE

Number of pages

22

Pages from-to

152-173

UT code for WoS article

000401388900013

EID of the result in the Scopus database

2-s2.0-85016719558