A Comprehensive Review on SAR of Curcumin

Abstract

Curcumin, a natural diaryl heptanoid continues to be used as an alternative medicinal agent in many parts of South East Asia for treatment of many ailments. It can be usually obtained from substituted aryl aldehydes and acetylacetone and this route enables synthesis of a diverse set of curcumin analogues. Numerous analogues have been synthesized and tested by several researchers to investigate their activity against known biological targets and to improve upon the pharmacological and ADME profile by modifying substitutions on aromatic rings, β-diketone moiety and two flanking double bonds conjugated to the β-diketone moiety. Successful synthesis of such derivatives with modifications has resulted in the development of potential anticancer candidates that target various stages in cancer cell growth and development. Based on the evidences in modifications of these three functional elements, we have attempted to summarize the structure activity relationship of molecules which can be further utilized by researchers in medicinal chemistry in exploring the structure of curcumin.

Curcumin Conjugates of Non‐steroidal Anti‐Inflammatory Drugs: Synthesis, Structures, Anti‐proliferative Assays, Computational Docking, and Inflammatory Response

“…Whereas potential health benefits of parent curcumin and its anticancer, anti-inflammatory, antioxidant, and anti-mutagenic effects have been extensively studied, [1][2][3][4][5] its complex signaling pathways and biological profile, coupled to poor pharmacokinetic properties have been major obstacles in developing a CUR-based anti-cancer drug, despite much effort to devise delivery methods by nanotechnology formulation or encapsula-tion into liposomes, or by inclusion into water soluble host molecules such as β-cyclodextrin. [6][7][8] Much work has been devoted to improving solubility, metabolic stability, lipophilicity, and other properties through synthesis of analogs, and these developments have been summarized in recent reviews.…”

Phytochemicals for the Management of Melanoma

“…Numerous analogs have been synthesized and are being tested against known biological targets to improve upon the pharmacological, absorption, distribution, metabolism and secretion profile by modifying substitutions on its aromatic rings, the β-diketone moiety, and the two flanking double bonds that are conjugated to the β-diketone moiety. This has led the way for researchers to further study the structure-activity relationship of curcumin in medicinal chemistry [209, 210]. Interestingly, Pisano et al [211] recently showed that a new curcumin analog alpha,beta-unsaturated ketone D6 [(3E,3'E)-4,4'-(5,5',6,6'-tetramethoxy-[1,1'-biphenyl]-3,3'-diyl)bis(but-3-en-2-one)] (Fig.…”

Hybrid Curcumin Compounds: A New Strategy for Cancer Treatment

“…Studies performed in vitro pointed out that this natural compound appears as an interesting epigenetic modulator [27,28] that possesses anti-oxidant [13,29,30], anti-inflammatory [31,32,33], anti-proliferative [34,35] and anti-angiogenic [36,37] properties in the micromolar concentration range in several cancer cell types. Curcumin’s structure-activity relationship was established by the comparison of the bioactivity of curcumin and its naturally occurring analogs, including its demethoxy derivatives (demethoxycurcumin and bisdemethoxycurcumin) and its active hydrogenated metabolites (tetrahydrocurcumin, hexahydrocurcumin and octahydrocurcumin) (Figure 1) [38,39,40], but also by the synthesis of curcumin analogs [41,42,43]. It became clear that the high anti-inflammatory and anti-tumor potentials of curcuminoids are related to their low level of hydrogenation and high level of methoxylation, but also to the high level of unsaturation of the diketone moiety [44].…”

“…The structure activity relationship (SAR) of curcumin was established based on the design and the analysis of the SAR and anticancer effect of curcumin-derived molecules [38,41,42,43,52]. Structural modifications of the curcumin scaffold were also elaborated in order to improve the low bioavailability of curcumin by increasing its hydrophilicity, by facilitating its transmembrane passage and increasing the delay of metabolism.…”