Substituted N-(Pyrazin-2-yl)benzenesulfonamides; Synthesis, Anti-Infective Evaluation, Cytotoxicity, and In Silico Studies

被引：12

作者：

Bouz, Ghada ^{[1
]}

Juhas, Martin ^{[1
]}

Otero, Lluis Pausas ^{[1
]}

de la Red, Cristina Paredes ^{[1
]}

Jan'ourek, Ondrej ^{[1
]}

Konecna, Klara ^{[1
]}

Paterova, Pavla ^{[2
]}

Kubicek, Vladimir ^{[1
]}

Janousek, Jiri ^{[1
]}

Dolezal, Martin ^{[1
]}

Zitko, Jan ^{[1
]}

机构：

[1] Charles Univ Prague, Fac Pharm Hradec Kralove, Heyrovskeho 1203, Hradec Kralove 50005, Czech Republic

[2] Univ Hosp, Dept Clin Microbiol, Sokolska 581, Hradec Kralove 50005, Czech Republic

来源：

MOLECULES | 2020年 / 25卷 / 01期

关键词：

anti-infectives; Mycobacterium tuberculosis; pyrazinamide; sulfonamide; target fishing; MYCOBACTERIUM-TUBERCULOSIS; DIHYDROPTEROATE SYNTHASE; PYRAZINE DERIVATIVES; SULFONAMIDES; INHIBITORS; MECHANISM; PHARMACOKINETICS; ANTIBACTERIAL; DESIGN;

D O I：

10.3390/molecules25010138

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We prepared a series of substituted N-(pyrazin-2-yl)benzenesulfonamides as an attempt to investigate the effect of different linkers connecting pyrazine to benzene cores on antimicrobial activity when compared to our previous compounds of amide or retro-amide linker type. Only two compounds, 4-amino-N-(pyrazin-2-yl)benzenesulfonamide (MIC = 6.25 mu g/mL, 25 mu M) and 4-amino-N-(6-chloropyrazin-2-yl)benzenesulfonamide (MIC = 6.25 mu g/mL, 22 mu M) exerted good antitubercular activity against M. tuberculosis H37Rv. However, they were excluded from the comparison as they-unlike the other compounds-possessed the pharmacophore for the inhibition of folate pathway, which was proven by docking studies. We performed target fishing, where we identified matrix metalloproteinase-8 as a promising target for our title compounds that is worth future exploration.

引用

页数：20

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