Synthesis and preliminary biological evaluation of resveratrol-like carbostyril derivatives as sirtuin 1 modulators and cyclooxygenase inhibitors.

Resveratrol is an antioxidant polyphenolic compound found in grape skins and red wine. It has been suggested that resveratrol mediates sirtuin 1 (SIRT1) activation, leading to anti-aging, life extension, and anti-cancer effects as demonstrated primarily in model organisms. Additionally, resveratrol inhibits cyclooxygenase-2 (COX-2), resulting in anti-inflammatory effects in atopic dermatitis and psoriasis as well as suppression of carcinogenesis. Thus, resveratrol is a pharmacologically multifunctional compound. However, it suffers from low oral bioavailability and a short half-life. Carbostyril (2-quinolinone, 2-quinolone) has been adopted as a structural scaffold in natural products as well as in pharmaceutical agents and physiologically active substances. The carbostyril scaffold is recognized for its biological stability and lack of toxicity. Consequently, replacing parts of lead or model compounds with carbostyril scaffolds as bioisosteres may generate promising pharmaceutical agents with reduced toxicity. In this study, we synthesized and biologically evaluated resveratrol-like carbostyril derivatives as SIRT1 modulators or COX inhibitors.