Synthesis and biological evaluation of 4-styrylcoumarin derivatives as inhibitors of TNF-α and IL-6 with anti-tubercular activity

• Published in: Bioorganic & medicinal chemistry letters 2011-04, Vol.21 (8), p.2547-2549
• Main Authors: Upadhyay, Kuldip, Bavishi, Abhay, Thakrar, Shailesh, Radadiya, Ashish, Vala, Hardevsinh, Parekh, Shrey, Bhavsar, Dhairya, Savant, Mahesh, Parmar, Manisha, Adlakha, Priti, Shah, Anamik
• Format: Article
• Language: English
• Subjects: 4-Styrylcoumarin; aldehydes; Anti-inflammatory activity; Anti-Inflammatory Agents - chemical synthesis; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - pharmacology; Anti-tubercular; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antitubercular Agents - chemical synthesis; Antitubercular Agents - chemistry; Antitubercular Agents - pharmacology; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; condensation; Coumarins - chemical synthesis; Coumarins - chemistry; Coumarins - pharmacology; IL-6; interleukin-6; Interleukin-6 - antagonists & inhibitors; Interleukin-6 - metabolism; Medical sciences; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Mycobacterium tuberculosis - drug effects; nuclear magnetic resonance spectroscopy; Pharmacology. Drug treatments; spectral analysis; TNF-α; tumor necrosis factor-alpha; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2011.02.016

A series of 4-styrylcoumarin have been synthesized by Knoevenagel condensation between substituted 4-methylcoumarin-3-carbonitrile and different heterocyclic or aromatic aldehydes. 4-Methylcoumarin-3-carbonitrile has been synthesized by the base catalyzed reaction between substituted 2-hydroxyacetophenone and ethyl cyanoacetate. The structures of the newly synthesized compounds were confirmed by 1H NMR, IR and mass spectral analysis. All the compounds were evaluated for their anti-inflammatory activity (against TNF-α and IL-6) and anti-tubercular activity. Compounds 6a, 6h and 6j exhibited promising activity against IL-6 with 72–87% inhibition and compound 6v showed potent activity against TNF-α with 73% inhibition at 10 μM concentration. Whereas compounds 6n, 6o, 6r and 6u showed very good anti-tubercular activity against Mycobacterium tuberculosis H37Rv strain at