Curcumin is a polyphenol derived from the root of turmeric (Curcuma longa) that it is widely used as a dietary spice and natural food colouring agent throughout the world.
The active principle in the root of the turmeric plant is the compound (1E,6E)-1,7-Bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione better known with its common name of Curcumin. This compound is formed by two sustituted phenyl ring connected by an unsaturated chain of 7 atoms (hepta-diene chain) comprising two proximal ketones group in keto-enolic equilibrium in solution. The enol form is one of the lowest energy conformers of the Curcumin. The structure shown in Figure 2 has been calculated using Quantum Mechanics optimization at Density Functional Theory level.
For its wide-ranged therapeutic applications (such as an antibiotic anti-inflammatory, anti-rheumatic, anti-arthritic, and antioxidant agent), curcumin finds its place in the Ayurveda, the traditional Indian medicine system.
Recent (and also controversial) studies have given pieces of evidence that curcumin has potent anticancer effects both alone or with other anticancer drugs. This has been tested in vivo and in vitro with melanoma, mantle cell lymphoma, hepatic, prostatic, ovarian, and pancreatic carcinomas. Curcumin has been reported to have diverse effects on signalling molecules involved in the regulation of the expression of angiogenesis-associated genes, activation of the apoptotic mechanisms, and induction of the cell cycle arrest. It also enhances the chemotherapeutic responses of cancer cells to several anticancer drugs. It is considered a potential inhibitor of the nuclear factor kappaB (NF-κB) signaling pathway. NF-κB promotes carcinogens in the liver, colon, lung, and leukemia and prostate cancer, and NF-κB excess is the main reason for the failure of chemotherapy with many drugs as well. Finally, curcumin also prevents the accumulation of amyloid-β (Aβ) aggregates as soluble oligomers, hence preventing Alzheimer’s disease.
Despite the aforementioned therapeutic potentials, low solubility in water and high degradation rate hinder the clinical development of curcumin. In fact, in vivo studies on rats have shown that its concentration in the blood rapidly decreases at the nanogram/millilitre level within 1 h even at very high dosage. This rapid degradation reduces its pharmacological efficacy, and for these reasons, there is a need to associate the drug with a delivering carrier to prevent these problems. Among various types of nanocarriers, block copolymer based ones are the most effective. These polymers are broadly used as drug-delivery systems, but the nature of this process is poorly understood.
For this reason, my research group in 2013 has developed a model of curcumin in the enolic form based on the GROMOS96 force field for molecular dynamics simulation . The model was used to test the binding to polyether-based block copolymers used for the design of polymeric micelle for drug delivery systems. In particular, we have studied curcumin in an aqueous solution of block copolymer based on polyethylene oxide (PEO) and polypropylene oxide (PPO). The study has been conducted in dimethoxyethane (DME) and 1,2-dimethoxypropane (DMP), the smallest PEO and PPO oligomers,
and in the presence of the block copolymer Pluronic P85 (PEO25-PPO40-PEO25).
In the DME and DMP aqueous mixture, the curcumin tends to be preferentially coated by the more hydrophobic DMP molecules. The same behaviour was observed in P85 solution that cluster around the curcumin with the hydrophobic PPO blocks wrapped around it and the terminal PEO blocks remain exposed to the water. This configuration provides evidence of a mechanism that can improve both the solvation and stability of curcumin in water. This also affects the mobility of the drug molecule by decreasing its diffusion coefficient. The formation of drug−polymer aggregation is observed within 100 ns of simulation. This noted condensing nuclei could be the first step to form the larger micelle observed in the experimental study reported in the literature.
- Samanta, D. Roccatano. Interaction of Curcumin with PEO-PPO-PEO block copolymers: A molecular dynamics study. J. Phys. Chem. B., 117(11), 3250-3257 (2013).