title: Molecular recognition and enhancement of aqueous solubility and bioactivity of CD437 by β-cyclodextrin.
abstract: CD437 (6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid) is a novel synthetic retinoic acid derivative that has been shown to selectively induce apoptosis in human lung cancer cells. This compound, however, is limited in its application due to its low solubility in aqueous solutions. One technique for increasing the solubility and bioavailability of a cytotoxic agent is the formation of inclusion complexes with cyclodextrins. Herein, we report the formation and characterization of a 2:1 complex between β-cyclodextrin (β-CD) and CD437. It is shown that CD437 is a tight binder of β-CD with an overall association constant of 2.6±0.6×10(7)M(-2). In addition, we demonstrate (a) that β-CD-derived complexation enhances the aqueous solubility of CD437, and (b) that a significant increase in the toxicity of CD437 against a human lung adenocarcinoma cell line can be achieved by co-treatment with β-CD.
authors.affiliation: Department of Medicine, Tulane University Health Sciences Center, 1430 Tulane Ave, New Orleans, LA 70112, United States.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Mishur
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Griffin
authors.forename: Cooper H
authors.initials: CH
authors.lastname: Battle
authors.forename: Bin
authors.initials: B
authors.lastname: Shan
authors.forename: Janarthanan
authors.initials: J
authors.lastname: Jayawickramarajah
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy; D000077192:Adenocarcinoma of Lung; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy; D008958:Models, Molecular; D012176:Retinoids / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D012995:Solubility; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; C099555:CD 437; D012176:Retinoids; D047392:beta-Cyclodextrins; C031215:betadex