Synthesis and pharmacological characterization of new curcumin ester pro-drugs with enhanced anti-inflammatory, anti-ulcerogenic and improved tissue distribution

Abstract

In this work, curcumin- Non steroidal anti-inflammatory drugs (NSAIDs) conjugates were synthesized by esterification of the phenolic group of curcumin with the acid group of NSAIDs using the Steglich esterification method to enhance the anti-inflammatory activity of curcumin and to reduce the gastrointestinal side effects of NSAIDs. A set of bis C-NSAIDs conjugates was prepared by direct coupling of curcumin with Aceclofenac and Diflunisal respectively in good yield and characterized by Fourier-transform infrared spectra (FTIR) and Proton Nuclear Magnetic Resonance Spectra (1HNMR). In vivo, studies were performed to evaluate the toxicity, anti-inflammatory activity, bio-distribution, and anti ulcerogenic studies of selected conjugates using different animal models. In Vivo studies reveal the enhanced biological activity with better tissue distribution of conjugates than that of parent curcumin and it could be a curcumin-based therapeutic molecule that might be explored further for its efficacy in managing inflammatory diseases.