Biological and pharmacological evaluation of dimethoxycurcumin: A metabolically stable curcumin analogue with a promising therapeutic potential

Abstract

Dimethoxycurcumin (DiMC) is a synthetic analog of curcumin with superior inter-related pro-oxidant and anti-cancer activity, and metabolic stability. Numerous studies have shown that DiMC reserves the biologically beneficial features, including anti-inflammatory, anticarcinogenic, and cytoprotective properties, almost to the same extent as curcumin exhibits. DiMC lacks the phenolic-OH groups as opposed to curcumin, dimethoxycurcumin, and bis-demethoxycurcumin that all vary in the number of methoxy groups per molecule, and has drawn the attentions of researchers who attempted to discover the structureactivity relationship (SAR) of curcumin. In this regard, tetrahydrocurcumin (THC), the reduced and biologically inert metabolite of curcumin, denotes the significance of the conjugated α,β diketone moiety for the curcumin activity. DiMC exerts unique molecular activities compared to curcumin, including induction of androgen receptor (AR) degradation and suppression of the transcription factor activator protein-1 (AP-1). The enhanced AR degradation on DiMC treatment suggests it as a novel anticancer agent against resistant tumors with androgenic etiology. Further, DiMC might be a potential treatment for acne vulgaris. DiMC induces epigenetic alteration more effectively than curcumin, although both showed no direct DNA hypomethylating activity. Given the metabolic stability, nanoparticulation of DiMC is more promising for in vivo effectiveness. However, studies in this regard are still in its infancy. In the current review, we portray the various molecular and biological functions of DiMC reported so far. Whenever possible, the efficiency is compared with curcumin and the reasons for DiMC being more metabolically stable are elaborated. We also provide future perspective investigations with respect to varying DiMC-nanoparticles. K E Y W O R D Sandrogen, anti-oxidant, curcumin, cytoprotective, dimethoxycurcumin, pro-oxidant

The Curcumin Analog CH-5 Exerts Anticancer Effects in Human Osteosarcoma Cells via Modulation of Transcription Factors p53/Sp1

“…Many in vitro and in vivo studies describe curcumin as a promising anticancer drug [ 15 , 16 , 17 , 18 ], but its instability and poor metabolic properties limit its clinical application [ 19 ]. Therefore, curcumin analogues are frequently investigated for improved chemical properties that still maintain its anticancer activity [ 21 , 34 ].…”

“…Although curcumin is considered a promising therapeutic agent for the treatment of different types of cancers, it is not physiologically stable and is not absorbed readily after ingestion [ 19 ]. This has driven the search for structural analogues with greater potency and bioavailability [ 20 , 21 ]. We have previously investigated the cytotoxic properties of a synthetic curcumin analog, 4,4′-[(2-Oxo-1,3-cyclohexanediylidene)-di(E)methylylidene] dibenzonitrile (named CH-5), in the human cancer gastric cell line HGC-27 [ 22 ].…”

Identification of the Multifaceted Chemopreventive Activity of Curcumin Against the Carcinogenic Potential of the Food Additive, KBrO3

“…For instance, a recent study has shown that dimethoxy curcumin has a unique anti-tumor activity due to its ability to suppress the transcription factor activator protein-1 (AP-1) and induce degradation of androgen receptors (AR). At the same time, dimethoxy curcumin showed a high metabolic stability compared to curcumin itself [ 88 ]. While another study found that a modification in curcumin’s aromatic ring resulted in the formation of 10 different curcumin analogues with more potent in vitro and in vivo anti-tumor activities than curcumin [ 89 ].…”

Inhibition of Curcumin on ZAKα Activity Resultant in Apoptosis and Anchorage- Independent Growth in Cancer Cells

“…Albeit curcumin elicits various biological activities in vivo, its undesirable physiochemical properties, such as low water solubility and poor bioavailability, are still problems (2). For applications in in vivo studies and clinical trails, many approaches have been undertaken like utilization of nano-base delivery systems and analogs (27).…”