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

Kód výsledku v 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>

Nalezeny alternativní kódy

RIV/00179906:_____/18:10383124

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

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

Návaznosti

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

Rok uplatnění

2018

Kód důvěrnosti údajů

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

Název periodika

Molecules

ISSN

1420-3049

e-ISSN

—

Svazek periodika

23

Číslo periodika v rámci svazku

9

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

17

Strana od-do

—

Kód UT WoS článku

000447365100301

EID výsledku v databázi Scopus

2-s2.0-85053621999