Two Cocrystals of Berberine Chloride with Myricetin and Dihydromyricetin: Crystal Structures, Characterization, and Antitumor Activities

Two novel drug–drug (1:1) cocrystals of berberine chloride (BER) with myricetin (MYR) and dihydromyricetin (DMY), BER-MYR(1), and BER-DMY(2) have been prepared and investigated systematically. The O–H···Cl– intermolecular interactions formed by hydroxyl groups of MYR and DMY with chloride anion dominated the formation of cocrystals 1 and 2. The values of energy gap (ΔE) and electrophilicity index (ω) computed by density functional theory calculations confirmed the chemical stability of molecules. Both cocrystals revealed low moisture adsorption up to 95% of relative humidity. The myricetin in cocrystal 1 revealed enhanced solubility in water. The two drugs in BER-MYR and BER-DMY cocrystals show synergistic anticancer effect in vitro.