The cocrystals of isorhamnetin and isoliquiritigenin with 4,4′-bipyridine: system characterization, stability, dissolution and anticancer activity

Abstract

As two natural products, isorhamnetin and isoliquiritigenin have been demonstrated to have significant anticancer activity. However, various pharmaceutical defects, such as low solubility and poor bioavailability, impede their anticancer efficacy. To optimize the anticancer efficacy of isorhamnetin and isoliquiritigenin, a scientific cocrystal design was performed to obtain two newly prepared cocrystals in this study. Leveraging multiple analytical techniques including single-crystal X-ray diffraction, powder X-ray diffraction, Fourier transform infrared spectroscopy, differential scanning calorimetry and thermogravimetric analysis, the isorhamnetin-4,4′-bipyridine (2 : 3) and isoliquiritigenin-4,4′-bipyridine (1 : 1) cocrystals were systematically characterized. The results of a series of evaluations on their stabilities, dissolution and anticancer activities demonstrated that these two cocrystals could remain stable under three different extreme environments, and the isorhamnetin-4,4′-bipyridine (2 : 3) cocrystal achieved significant improvement in solubility, dissolution rate and anticancer efficacy compared to isorhamnetin. For the isoliquiritigenin-4,4′-bipyridine (1 : 1) cocrystal, there was no increase in its solubility and dissolution rate compared to isoliquiritigenin. Nevertheless, a slight increase in the anticancer activity of isoliquiritigenin was achieved by the formation of the cocrystal. This study was a meaningful investigation, which not only laid an innovative material foundation for the development of isorhamnetin and isoliquiritigenin but also provided a new strategy to optimize the pharmaceutical properties of natural products.