title: 4'-O-Alkyaloenin derivatives and their sulfates directed toward overcoming multidrug resistance in tumor cells.
abstract: The cytotoxic effects on HCT 116, Hep G2 and HCT 116/VCR 100-1-1 cell lines of synthetic 4'-O-alkylaloenins (2-17), 4'-O-benzylaloenin (18) and 4'-O-allylaloenin (19) were examined by MTT assay, and compared with that of aloenin (1) isolated from Aloe arborescens Mill. Var. natalensis Berger which showed no marked effect (IC50 value: > 100 microM). The cytotoxic effects of 4'-O-alkylaloenin sulfates (21-29) were also examined on the same cell lines. The introduction of a longer alkyl group at the O-4' position of 1 resulted in a higher cytotoxic action on HCT 116 and Hep G2 cells. Among 4'-O-alkylaloenins 2-17, 4'-O-tetradecylaloenin 14 was the most cytotoxic to both on HCT 116 cells (IC50 value: 5.3+/-2.3 microM) and Hep G2 cells (IC50 value: 4.0+/-0.6 microM). Also among 4'-O-alkylaloenin sulfates 21-29, 4'-O-dodecylaloenin sulfate 29 was the most cytotoxic to both on HCT 116 (IC50 value: 4.8+/-0.2 microM) and Hep G2 cells (IC50 value: 4.0+/-0.5 microM). 4'-O-Alkylaloenins 7-14 and 4'-O-alkylaloenin sulfates 24-29 were also cytotoxic to Hep G2 and HCT 116/VCR 100-1-1 cell lines, which overexpress P-glycoprotein, as well as HCT 116 cell lines which scarcely express it.
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University, Keyakidai 1-1, Sakado, Saitama 350-0295, Japan.
authors.forename: Guang-Zhu
authors.initials: GZ
authors.lastname: Jin
authors.forename: Hong-Ji
authors.initials: HJ
authors.lastname: Quan
authors.forename: Jyunichi
authors.initials: J
authors.lastname: Koyanagi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Takeuchi
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Miura
authors.forename: Fusao
authors.initials: F
authors.lastname: Komada
authors.forename: Setsuo
authors.initials: S
authors.lastname: Saito
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D015179:Colorectal Neoplasms; D004396:Coloring Agents / Q000737:chemistry; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005960:Glucosides / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology; D013431:Sulfates; D013778:Tetrazolium Salts / Q000737:chemistry; D013844:Thiazoles / Q000737:chemistry; D014407:Tumor Cells, Cultured
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004396:Coloring Agents; D005960:Glucosides; D013431:Sulfates; D013778:Tetrazolium Salts; D013844:Thiazoles; C033526:aloenin; C022616:thiazolyl blue