Design, Synthesis and Evaluation of N-pyrazinylbenzamides as Potential Antimycobacterial Agents

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F18%3A10383124" target="_blank" >RIV/00216208:11160/18:10383124 - isvavai.cz</a>

Alternative codes found

RIV/00179906:_____/18:10383124

Result on the web

<a href="http://www.mdpi.com/1420-3049/23/9/2390/htm" target="_blank" >http://www.mdpi.com/1420-3049/23/9/2390/htm</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/molecules23092390" target="_blank" >10.3390/molecules23092390</a>

Result language

angličtina

Original language name

Design, Synthesis and Evaluation of N-pyrazinylbenzamides as Potential Antimycobacterial Agents

Original language description

Three series of N-(pyrazin-2-yl)benzamides were designed as retro-amide analogues of previously published N-phenylpyrazine-2-carboxamides with in vitro antimycobacterial activity. The synthesized retro-amides were evaluated for in vitro growth inhibiting activity against Mycobacterium tuberculosis H37Rv (Mtb), three non-tuberculous mycobacterial strains (M. avium, M. kansasii, M. smegmatis) and selected bacterial and fungal strains of clinical importance. Regarding activity against Mtb, most N-pyrazinylbenzamides (retro-amides) possessed lower or no activity compared to the corresponding N-phenylpyrazine-2-carboxamides with the same substitution pattern. However, the active retro-amides tended to have lower HepG2 cytotoxicity and better selectivity. Derivatives with 5-chloro substitution on the pyrazine ring were generally more active compared to their 6-cloro positional isomers or non-chlorinated analogues. The best antimycobacterial activity against Mtb was found in N-(5-chloropyrazin-2-yl)benzamides with short alkyl (2h: R-2 = Me; 2i: R-2 = Et) in position 4 of the benzene ring (MIC = 6.25 and 3.13 mu g/mL, respectively, with SI &gt; 10). N-(5-Chloropyrazin-2-ylbenzamides with hydroxy substitution (2b: R-2 = 2-OH; 2d: R-2 = 4-OH) on the benzene ring or their acetylated synthetic precursors possessed the broadest spectrum of activity, being active in all three groups of mycobacterial, bacterial and fungal strains. The substantial differences in in silico calculated properties (hydrogen-bond pattern analysis, molecular electrostatic potential, HOMO and LUMO) can justify the differences in biological activities between N-pyrazinylbenzamides and N-phenylpyrazine-2-carboxamides.

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

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

2018

Confidentiality

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

Name of the periodical

Molecules

ISSN

1420-3049

e-ISSN

—

Volume of the periodical

23

Issue of the periodical within the volume

9

Country of publishing house

CH - SWITZERLAND

Number of pages

17

Pages from-to

—

UT code for WoS article

000447365100301

EID of the result in the Scopus database

2-s2.0-85053621999