Structure and activity relationship of curucmin: role of methoxy group in anti‐inflammatory and anti‐colitis effects of curcumin

Abstract

Substantial studies have shown that curcumin, a dietary compound from Turmeric, has beneficial effects on inflammatory diseases such as inflammatory bowel disease (IBD). A better understanding of structure‐activity relationship (SAR) of curcumin could help us to apprehend its molecular mechanism, and design better curcumin‐based drugs. While most previous studies have focused on the thiol‐reactive α,β‐unsaturated carbonyl groups of curcumin, little is known about the roles of methoxy groups in biological activities of curcumin. Here we synthesized a series of curcumin analogs with different substitution groups (R = H‐, Br‐, Cl‐, F‐, NO2‐, CH3‐, and OH‐) to replace the methoxy group, and evaluated their biological effects on inflammatory responses and NF‐κB signaling in RAW 264.7 macrophage cells, and dextran sulfate sodium (DSS)‐induced colitis in C57BL/6 mice. The analogs have dramatically different effects on inflammation in vitro and in vivo, supporting that the substitution group on the methoxy position plays an important role in the anti‐inflammatory effects of curcumin. The methoxy group is a potential structural candidate to modify, in order to design curcumin‐based drugs for inflammatory diseases.Support or Funding Informationnew faculty start‐up fund, Armstrong Fund of Science Award from University of Massachusetts Amherst and USDA NIFA 2016‐67017‐24423