title: Properties of Ultraviolet Exposed Camptothecin Studied by Using Optical Spectroscopy Methods.
abstract: Camptothecin (CPT) and its analogs as inhibitors of topoisomerase I are anticancer compounds. Their antitumor potency is seriously limited due to hydrolysis of lactone form of camptothecins in solutions at pH>5.5, which leads to the formation of inactive carboxylate form with open lactone ring. Furthermore, the clinical application of CPT is also restricted by strong affinity of its carboxylate form to human serum albumin which destabilizes the active lactone form. By UV irradiation of the CPT carboxylate authors of this paper received camptothecin compound which has biophysical properties similar to the lactone form. The specific objective of the project is to determine the properties using the methods of absorption and steady-state fluorescence spectra analysis, fluorescence lifetime measurements as well as steady-state fluorescence anisotropy. The results suggest that the UV exposed camptothecin carboxylate changes the chemical structure. The high-throughput assays based on the steady state fluorescence anisotropy measurements proved that the form obtained as a result of UV irradiation of CPT carboxylate exhibits weaker affinity to albumin than CPT carboxylate however stronger than CPT lactone. This property is very desirable from the point of view of clinical applications.
authors.affiliation: Medical Physics Division, Biophysics Department, Faculty of Pharmacy, Collegium Medicum of Nicolaus Copernicus University, Jagiellonska 13, PL-85-067 Bydgoszcz, Poland. blanka@cm.umk.pl.
authors.forename: Blanka
authors.initials: B
authors.lastname: Ziomkowska
authors.forename: Tomasz
authors.initials: T
authors.lastname: Wybranowski
authors.forename: Michal
authors.initials: M
authors.lastname: Cyrankiewicz
authors.forename: Stefan
authors.initials: S
authors.lastname: Kruszewski
mesh_terms: D002166:Camptothecin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000528:radiation effects; D002264:Carboxylic Acids / Q000378:metabolism; D004264:DNA Topoisomerases, Type I; D005454:Fluorescence Polarization; D006801:Humans; D007783:Lactones / Q000378:metabolism; D012709:Serum Albumin / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D059004:Topoisomerase I Inhibitors; D014466:Ultraviolet Rays
chemical_list: D002264:Carboxylic Acids; D007783:Lactones; D012709:Serum Albumin; D059004:Topoisomerase I Inhibitors; D004264:DNA Topoisomerases, Type I; C528909:TOP1 protein, human; D002166:Camptothecin