Synthetic strategies in curcumin chemistry focused on anticancer applications

Abstract

In spite of having received considerable interest as a potential anticancer agent over the past two decades, curcumin has not been developed into a sturdy drug candidate yet, mainly due to the challenges imposed by its rapidly metabolizable structure, leading to bioavailability and stability issues, and its aspecific activity. To circumvent these obstacles, chemical modification of the parent scaffold has been shown to involve an eligible approach for the construction of curcuminoids with improved properties. This review article provides a compilation of curcumin modifications and the effect thereof on the anticancer activity displayed by the resulting new analogs.

Molecular Docking, Synthesis and <i>In Vitro</i> Antiplasmodium Assay of Monoketone Curcumin Analogous from 2-Chlorobenzaldehyde

“…According to Table 3, the molecular weight of the analogous 3, 4, and 6 ranged from 343.25 to 434.36 g/mol, the amount of HBA ranged from 1 to 2, the amount of HBD ranged from 0 to 1 and the log P value ranged from 4.33 to 5.66. While the curcumin analogue 4 met the Lipinski Rules of Five, the analogues 3 and 4 violated one parameter of log P. Chander et al [31] also stated that 95% of clinically approved drugs had the following range of physicochemical properties: molecular weight (130-725), HA (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20), HD (0-6) and log P (−2 to 6.5). Therefore, all the analogous 3, 4, and 6 met the physicochemical properties as stated in the previous study [31].…”

“…Curcumin is one of the natural compounds that has been reported to have many bioactivities such as anticancer, antidiabetic, anti-inflammatory, antiviral, antimicrobial, antioxidant, and antiplasmodium [3]. A previous study showed that curcumin extract has good in vitro antiplasmodium activity with an IC 50 value of 3.5 μg/mL [4].…”

“…Apart from the interesting biological activities, the applications of curcumin as a drug were limited due to its low bioavailability. The presence of unstable methylene and β-diketone groups in the structure of curcumin led to poor absorption, a high rate of metabolism, inactivity of metabolic products and rapid elimination from the body [3,5]. One of the strategies to improve curcumin bioavailability was by modifying the β-diketone group of curcumin into the monoketone group [6].…”

Curcumin‐based bioactive heterocycles derived via multicomponent reactions

“…[ 123–126 ] Synthetic manipulations on curcumin to obtain curcumin based heterocyclic compounds via MCR approach generates the molecules of enhanced therapeutic potential. [ 127 ]…”

“…[123][124][125][126] Synthetic manipulations on curcumin to obtain curcumin based heterocyclic compounds via MCR approach generates the molecules of enhanced therapeutic potential. [127] Sahu et al [42] reported curcumin-based 4H-pyrimido [ 4) displays potent activity against fungal and bacterial strains. [53] The antibacterial activity of compounds 56 (MIC: 30.8 µM/mL), 58 (MIC: 28.6 µM/mL), 59 (MIC: 25.7 µM/mL), and 62 (MIC: 28.5 µM/mL) were most active against bacterial strain Bacillus cereus as compared to standard drug ampicillin (MIC: 38 µM/mL).…”