Novel derivatives of nitro-substituted salicylic acids: Synthesis, antimicrobial activity and cytotoxicity

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• 作者：Georgios Paraskevopoulos^a ; Martin Krá ; tký ; ^a ; Jana Mandí ; ková ; ^b ; Franti&scaron ; ek Trejtnar^b ; Jiřina Stolaří ; ková ; ^c ; Petr Pá ; vek^b ; Gurdyal Besra^d ; Jarmila Vin&scaron ; ová ; ^a ; ^{jarmila.vinsova@faf.cuni.cz" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Salicylanilides ; Nitro group ; In silico ADMET prediction ; In vitro antimycobacterial activity ; In vitro antimicrobial activity ; Cytotoxicity
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2015
• 出版时间：15 November 2015
• 年：2015
• 卷：23
• 期：22
• 页码：7292-7301
• 全文大小：616 K

文摘

Inspired by the high antituberculous activity of novel nitro-substituted derivatives and based on promising predicted ADMET properties we have synthesized a series of 33 salicylanilides containing nitro-group in their salicylic part and evaluated them for their in vitro antimycobacterial, antimicrobial and antifungal activities. The presence of nitro-group in position 4 of the salicylic acid was found to be beneficial and the resulting molecules exhibited minimum inhibitory concentrations (MICs) ranging from 2 to 32 μM against Mycobacterium tuberculosis. The best activity was found for 2-hydroxy-4-nitro-N-[4-(trifluoromethyl)phenyl]benzamide (MIC = 2 μM). 4-Nitrosalicylanilides were also found to be active against all Staphylococcus species tested while for MRSA strain 2-hydroxy-4-nitro-N-[4-(trifluoromethyl)phenyl]benzamide’s MIC was 0.98 μM. None of the nitrosalicylanilides was active against Enterococcus sp. J 14365/08 and no considerable activity was found against Gram-negative bacteria or fungi. The hepatotoxicity of all nitrosalicylanilides was found to be in the range of their MICs for HepG2 cells.