Avidin has synthesized more than 70 curcumin analogs that have been optimized to have anti-cancerous properties in tumor models. Later these molecules showed promising anti-inflammatory activity in rat colitis models. The synthesis of the lead molecule can be easily scaled up
The anti-inflammatory role of Mannich curcuminoids, with special focus on colitis, was recently published by our team. Mannich curcuminoids (C142 or C150) have powerful anti-inflammatory activity in the TNBS (2,4,6-trinitrobenzenesulphonic acid) induced colitis rat model. Treatment with C142 or C150 reduced leukocyte infiltration in the submucosa and muscular propria of the inflamed bowels; moreover, they decreased body weight loss and caused 25% decrease in the severity of colonic inflammation and the hemorrhagic lesion sizes. The colonic myeloperoxidase (MPO) activity (as an indicator of intense neutrophil infiltration) was also decreased by 50%. Lipopolysaccharide (LPS) co-treatment with Mannich curcuminoids inhibited the NF-κB activity (nuclear factor kappa B) on a concentration dependent manner in an NF-κB-driven luciferase expressing reporter cell line. The lead molecule, C150 exerted a profound inhibition of the expression of inflammatory cytokines; tumor necrosis factor-α (TNF-α) interleukin-6 (IL-6) and interleukin-4 (IL-4) in human peripheral blood mononuclear cells (PBMC) upon LPS stimulus.
In addition to its anti-inflammatory activity, we previously reported that the Mannich curcuminoids also have in vivo anticancer effects in lung carcinoma and glioma xenograft models, and in vitro in pancreatic cancer cell line.
The proposed main indication of lead compounds is chronic inflammatory bowel disease; however, our new analogues showed impressive effectiveness in xenograft cancer models. Moreover, the application could be wider than what cellular and animal studies currently suggest — including the treatment of other inflammatory diseases.