Novel salicylanilides from 4,5-dihalogenated salicylic acids: Synthesis, antimicrobial activity and cytotoxicity

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• 作者：Georgios Paraskevopoulos^a ; Sara Monteiro^b ; Rudolf Vosá ; tka^c ; Martin Krá ; tký ; ^c ; Lucie Navrá ; tilová ; ^d ; Franti&scaron ; ek Trejtnar^d ; Jiřina Stolaří ; ková ; ^e ; Jarmila Vin&scaron ; ová ; ^c ; ^{jarmila.vinsova@faf.cuni.cz}
• 关键词：Salicylanilides ; Double halogenation ; Tuberculosis ; In vitro antimycobacterial activity ; Cytotoxicity
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2017
• 出版时间：15 February 2017
• 年：2017
• 卷：25
• 期：4
• 页码：1524-1532
• 全文大小：670 K
• 卷排序：25

文摘

Salicylanilides have proved their activity against tuberculosis (TB). One weak electron-withdrawing substituent is favored at the salicylic part, specially Cl or Br atoms at positions 4 or 5. On the other hand, the antimycobacterial activity of salicylanilides is negatively affected when a strong electron-withdrawing substituent (NO2) is present at the same positions. Herein we describe the synthesis and characterization of novel salicylanilides possessing two weak electron-withdrawing groups (halogen atoms) at their salicylic part and compare their antitubercular activity with their monohalogenated analogues. All dihalogenated derivatives proved to possess antitubercular activity at a very narrow micromolar range (MIC = 1–4 μM), similar with their most active monohalogenated analogues. More importantly, the most active final molecules were further screened against multidrug resistant strains and found to inhibit their growth at the range of 0.5–4 μM.