Combating highly resistant emerging pathogen Mycobacterium abscessus and Mycobacterium tuberculosis with novel salicylanilide esters and carbamates

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F71009396%3A_____%2F15%3AN0000008" target="_blank" >RIV/71009396:_____/15:N0000008 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11160/15:10312612

Result on the web

<a href="https://www.sciencedirect.com/science/article/abs/pii/S0223523415301331" target="_blank" >https://www.sciencedirect.com/science/article/abs/pii/S0223523415301331</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ejmech.2015.07.001" target="_blank" >10.1016/j.ejmech.2015.07.001</a>

Result language

angličtina

Original language name

Combating highly resistant emerging pathogen Mycobacterium abscessus and Mycobacterium tuberculosis with novel salicylanilide esters and carbamates

Original language description

In the Mycobacterium genus over one hundred species are already described and new ones are periodically reported. Species that form colonies in a week are classified as rapid growers, those requiring longer periods (up to three months) are the mostly pathogenic slow growers. More recently, new emerging species have been identified to lengthen the list, all rapid growers. Of these, Mycobacterium abscessus is also an intracellular pathogen and it is the most chemotherapy-resistant rapid-growing mycobacterium. In addition, the cases of multidrug-resistant Mycobacterium tuberculosis infection are also increasing. Therefore there is an urgent need to find new active molecules against these threatening strains. Based on previous results, a series of salicylanilides, salicylanilide 5-chloropyrazinoates and carbamates was designed, synthesized and characterised. The compounds were evaluated for their in vitro activity on M. abscessus, susceptible M. tuberculosis H(37)Rv, multidrug-resistant (MDR) M. tuberculosis MDR A8, M. tuberculosis MDR 9449/2006 and on the extremely-resistant Praha 131 (XDR) strains. All derivatives exhibited a significant activity with minimum inhibitory concentrations (MICs) in the low micromolar range. Eight salicylanilide carbamates and two salicylanilide esters exhibited an excellent in vitro activity on M. abscessus with MICs from 0.2 to 2.1 mu M, thus being more effective than ciprofloxacin and gentamicin. This finding is potentially promising, particularly, as M. abscessus is a threateningly chemotherapy-resistant species. M. tuberculosis H(37)Rv was inhibited with MICs from 0.2 mu M, and eleven compounds have lower MICs than isoniazid. Salicylanilide esters and carbamates were found that they were effective also on MDR and XDR M. tuberculosis strains with MICs >= 1.0 mu M. The in vitro cytotoxicity (IC50) was also determined on human MonoMac-6 cells, and selectivity index (SI) of the compounds was established. In general, salicylanilide derivatives substituted by halogens on both salicyl and aniline rings showed better activity, than 4-benzoylaniline derivatives. The ester or carbamate bond formation of parent salicylanilides mostly retained or improved antimycobacterial potency with moderate selectivity.

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

30104 - Pharmacology and pharmacy

Project

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Continuities

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Publication year

2015

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

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Volume of the periodical

101

Issue of the periodical within the volume

August

Country of publishing house

FR - FRANCE

Number of pages

13

Pages from-to

692-704

UT code for WoS article

000360771900059

EID of the result in the Scopus database

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