Synthesis and evaluation of diverse thio avarol derivatives as potential UVB photoprotective candidates

• Published in: Bioorganic & medicinal chemistry letters Vol. 17; no. 9; pp. 2561 - 2565
• Main Authors: Amigó, María, Terencio, María C., Payá, Miguel, Iodice, Carmine, Rosa, Salvatore De
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.05.2007; Elsevier
• Subjects: Antioxidants - pharmacology; Biological and medical sciences; Cell Line, Tumor; Chemistry, Pharmaceutical - methods; Drug Design; Humans; Keratinocytes; Magnetic Resonance Spectroscopy; Medical sciences; Models, Chemical; Molecular Conformation; Neutrophils - drug effects; NF-kappa B - antagonists & inhibitors; NF-κB; Pharmacology. Drug treatments; Photochemistry - methods; Reactive Oxygen Species; Sesquiterpenes - chemical synthesis; Sesquiterpenes - pharmacology; Skin, nail, hair, dermoskeleton; Thio avarol derivatives; TNF-α; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Ultraviolet Rays; UVB; UVB; Keratinocytes; NF-κB; TNF-α; Thio avarol derivatives; Diphenols; Organic sulfide; Hydroquinone derivatives; Structure activity relation; Sesquiterpenes; Bicyclic compound; Keratinocyte; Transcription factor NFκB; Inhibition; Chemical synthesis; Protection; Tumor necrosis factor α; Hemisynthesis; Human; Terpenoid; Photoprotector; UVB radiation; Benzene derivatives; Cytokine; NF-KB; Antioxidant; In vitro; Photodermatosis; Position isomer; Cell line; Cytoprotector; Phenols; Skin; Neutrophil
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2007.02.007

Semisynthesis of 13 new thio avarol derivatives ( 4– 16) and in vitro evaluation on the photodamage response induced by UVB irradiation are described. Their ability to inhibit NF-κB activation and TNF-α generation in HaCaT cells as well as their antioxidant capacity in human neutrophils has been also reported. Semisynthesis of 13 new thio avarol derivatives ( 4– 16) and in vitro evaluation on the photodamage response induced by UVB irradiation are described. Their ability to inhibit NF-κB activation and TNF-α generation in HaCaT cells as well as their antioxidant capacity in human neutrophils has also been studied. Among them we have identified two monophenyl thio avarol derivatives ( 4– 5) lacking cytotoxicity which can be considered promising UVB photoprotective agents through the potent inhibition of NF-κB activation with a mild antioxidant pharmacological profile.