Perspectives on New Synthetic Curcumin Analogs and their Potential Anticancer Properties

Abstract

Curcumin is the active component of dried rhizome of Curcuma longa, a perennial herb belonging to ginger family, cultivated extensively in south and southeastern tropical Asia. It is widely consumed in the Indian subcontinent, south Asia and Japan in traditional food recipes. Extensive research over last few decades has shown that curcumin is a potent anti-inflammatory agent with powerful therapeutic potential against a variety of cancers. It suppresses proliferation and metastasis of human tumors through regulation of various transcription factors, growth factors, inflammatory cytokines, protein kinases and other enzymes. It induces apoptotic cell death and also inhibits proliferation of cancer cells by cell cycle arrest. Pharmacokinetic data has shown that curcumin undergoes rapid metabolism leading to glucuronidation and sulfation in the liver and excretion in the feces, which accounts for its poor systemic bioavailability. The compound has, therefore, been formulated and administered using different drug delivery systems such as liposomes, micelles, polysaccharides, phospholipid complexes and nanoparticles that can overcome the limitation of bioavailability to some extent. Attempts to avoid rapid metabolism of curcumin until now have been met with limited success. This has prompted researchers to look for new synthetic curcumin analogs in order to overcome the drawbacks of limited bioavailability and rapid metabolism, and gain efficacy with reduced toxicity. In this review we provide a summarized account of novel synthetic curcumin formulations and analogs, and the recent progress in the field of cancer prevention and treatment.

Molecular Mimics of Classic P-Glycoprotein Inhibitors as Multidrug Resistance Suppressors and Their Synergistic Effect on Paclitaxel

“…Many of the reported analogues of curcumin are either arylvinylketones or bis-(arylvinyl)ketones. The curcumin analogues that did not adhere to the 7-atom linker rule kept good to excellent Pgp inhibition activities [30]. …”

Curcumin-enhanced chemosensitivity of FDA-approved platinum (II)-based anti-cancer drugs involves downregulation of nuclear endonuclease G and NF-κB as well as induction of apoptosis and G2/M arrest

“…As a result, several strategies have been developed to improve its bioavailability, including the development of curcumin predrugs and structural analogues, blocking the metabolic pathways of curcumin using adjuvants, increasing the solubility of curcumin by forming phospholipid complexes or PEGylation, and promoting absorption using a delivery system involving carrier vehicles, such as polymer nanoparticles, liposomes, phytosomes and surfactant micelles (Anand et al, 2008;Vyas et al, 2013). It is noteworthy that the addition of adjuvant piperine, an inhibitor of glucuronidation of curcumin, has been demonstrated to increase 150% bioavailability of curcumin in rats and 2000% in man (Anand et al, 2008).…”

Cancer-selective cytotoxic Ca2+ overload in acute myeloid leukemia cells and attenuation of disease progression in mice by synergistically acting polyphenols curcumin and carnosic acid

“…However, low bioavailability of these agents limits their therapeutic application, and the concentrations needed for retardation of tumor growth in rodents greatly exceed doses compatible with human use [27–29]. The utilization of the ability of polyphenols to synergistically enhance anticancer effects of one another in different models [30–33] has been suggested, among other approaches [28, 34], to improve their bioactivity in vivo . Using this combination strategy, we have previously shown that CUR and another polyphenol, carnosic acid (CA), combined at potentially bioavailable non-cytotoxic concentrations of each agent robustly triggered apoptosis in KG-1a and HL60 AML cells [35].…”