title: 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, anti-carcinogenic, 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 structure-activity 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.
authors.affiliation: Biotechnology Research Center, Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Manouchehr
authors.initials: M
authors.lastname: Teymouri
authors.affiliation: Biotechnology Research Center, Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Nastaran
authors.initials: N
authors.lastname: Barati
authors.affiliation: Department of Medicine, Unit of Internal Medicine, Angiology and Arteriosclerosis Diseases, University of Perugia, Perugia, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Pirro
authors.affiliation: Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.|Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Amirhosein
authors.identifier: http://orcid.org/0000-0002-8656-1444
authors.initials: A
authors.lastname: Sahebkar
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D003474:Curcumin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D004339:Drug Compounding; D004355:Drug Stability; D006801:Humans; D015394:Molecular Structure; D053758:Nanoparticles; D018384:Oxidative Stress / Q000187:drug effects; D059748:Proteolysis; D011944:Receptors, Androgen / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D011944:Receptors, Androgen; D018808:Transcription Factor AP-1; C521105:dimethoxycurcumin; D003474:Curcumin
keywords: androgen; anti-oxidant; curcumin; cytoprotective; dimethoxycurcumin; pro-oxidant