ABSTRACT
The inclusion complex of GA-13316 with ß-cyclodextrin (ß-CD) is one of a unique series of gibberellin derivatives possessed of potential anticancer activities. The complex with ß-CD was characterized by means of UV, XRD, DSC, TG, (1)H, and 2D NMR spectroscopy. In addition, we investigated the main aspects of the interaction between GA-13316 and ß-CD using both experimental and molecular modeling approaches. The complex still maintained its anticancer activity, as shown by in vitro cell survival assay on the human colon carcinoma cell line (HCT116) and the human lung cancer cell line (H460). The results showed that the use of ß-CD could be obviously improved the water solubility and stability of GA-13316, implying that the inclusion complex could be a promising future therapeutic agent.
Subject(s)
Antineoplastic Agents/administration & dosage , Antineoplastic Agents/chemistry , Gibberellins/administration & dosage , Gibberellins/chemistry , beta-Cyclodextrins/chemistry , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Colonic Neoplasms/drug therapy , Gibberellins/pharmacology , Humans , Lung Neoplasms/drug therapy , Magnetic Resonance Spectroscopy , Molecular Docking Simulation , SolubilityABSTRACT
GA-13315 (13-chlorine-3,15-dioxy-gibberllic acid methyl ester) was semi-synthesized by GA3 (gibberellic acid) as a potential anticancer drug. To pursue its promising application, cyclodextrin was used for forming complexes to overcome its drawbacks such as poor water solubility and stability. So, GA-13315/CD complexes were prepared with native ß-cyclodextrin and its derivatives (hydroxypropyl-ß-cyclodextrin (HPßCD)) and their inclusion complexation behavior, characterization and binding ability in both solution and the solid state was studied by means of UV, XRD, DSC, SEM, (1)H and 2D NMR spectroscopy. Furthermore, preliminary in vitro cytotoxicity assay showed that the complexes still maintain antitumor activities, compared with GA-13315 or adriamycin (ADM, positive control) as the positive control. The results showed that the water solubility and stability of GA-13315 were obviously improved in the inclusion complex with cyclodextrins, suggesting the inclusion complexes as promising future therapeutic agents.
