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 (Δ E ) 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 .