title: Design and QSAR study of analogs of alpha-tocopherol with enhanced antiproliferative activity against human breast adenocarcinoma cells.
abstract: Quantitative structure-activity relationships (QSAR) have been established for two sets of the antitumor drugs, alpha-tocopherol derivatives. Constitutional, geometrical, physico-chemical and electronic descriptors (using the B3LYP/6-31G (d, p) basis set) were computed and analyzed. The most relevant of these descriptors were grouped and multiple linear regressions have been carried out. QSAR model with four variables, R2=0.98 and cross-validation parameter qpre2)=0.91, was selected. Analogs of alpha-tocopherol (compounds D-1 and D-2) have been designed and their antiproliferative activities were evaluated using the proposed regression model. Calculated antiproliferative activities of the designed lysine/alpha-tocopherol/cholesterol conjugates, IC50 (D-1)=2.25 microM and IC50 (D-2)=3.42 microM, were significantly stronger than activities of the other analyzed compounds IC50>4 microM.
authors.affiliation: Department of Medicinal Chemistry, Pharmacy Faculty, University of Belgrade, Vojvode Stepe 450, 11000 Belgrade, Serbia. katarina.nikolich@gmail.com
authors.forename: K M
authors.initials: KM
authors.lastname: Nikolic
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D021281:Quantitative Structure-Activity Relationship; D012044:Regression Analysis; D024502:alpha-Tocopherol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D024502:alpha-Tocopherol