Enhancement of the Biological Activity of Catechin from Uncaria gambir as Anticancer Agents through Molecular Encapsulation Studies: Experimental and Computational Approaches

Catechin, a bioactive flavonoid derived from Uncaria gambir, exhibits significant anticancer potential but is limited by its poor aqueous solubility and low bioavailability. To overcome these challenges, this study investigates the molecular encapsulation of catechin with β-cyclodextrin (βCD) and hydroxypropyl-β-cyclodextrin (HPβCD) through experimental and computational approaches. Structural characterisation using field emission scanning electron microscopy (FESEM), X-ray diffraction (XRD) and nuclear magnetic resonance (NMR) spectroscopy confirmed the successful formation of inclusion complexes, with HPβCD exhibiting superior amorphisation and molecular dispersion, suggesting enhanced solubility. Additionally, in silico molecular studies through molecular docking and molecular dynamics simulations of the inclusion complexes were conducted. The results demonstrate no significant change in the coordinates of catechin inside the cavities of both materials. In particular, the Cat-HPβCD complex exhibited stronger binding free energy (∆Gbind) through several end-point free energy approaches estimated in this research. Furthermore, Cat-HPβCD complex shows a significant cytotoxic effect against MCF-7 breast cancer cells time-dependent, achieving IC50 values of 14 μg/mL and 10 μg/mL at 48 and 72 hours, respectively. These findings highlight HPβCD as an optimal carrier for catechin, enhancing its solubility, stability, and anticancer efficacy, paving the way for its potential pharmaceutical applications.