title: Solid-Phase synthesis of a library constructed of aromatic phosphate, long alkyl chains and tryptophane components, and identification of potent dipeptide telomerase inhibitors.
abstract: Telomerase inhibitors are expected as a new candidate of therapeutic agents for cancer. Recently, we have found novel inhibitors based on the bisindole skeleton. In this study, solid-phase synthesis was applied to construct a library of inhibitors having aromatic phosphate, long alkyl chain and tryptophane components, from which a D,D-ditryptophane derivative has been identified as a new potent telomerase inhibitor with IC(50) values of 0.3 microM. A hypothetical binding model for the new inhibitors has been proposed based on the structure-activity relationship.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. sasaki@phar.kyushu-u.ac.jp
authors.forename: S
authors.initials: S
authors.lastname: Sasaki
authors.forename: T
authors.initials: T
authors.lastname: Ehara
authors.forename: M R
authors.initials: MR
authors.lastname: Alam
authors.forename: Y
authors.initials: Y
authors.lastname: Fujino
authors.forename: N
authors.initials: N
authors.lastname: Harada
authors.forename: J
authors.initials: J
authors.lastname: Kimura
authors.forename: H
authors.initials: H
authors.lastname: Nakamura
authors.forename: M
authors.initials: M
authors.lastname: Maeda
mesh_terms: D004151:Dipeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D013329:Structure-Activity Relationship; D019098:Telomerase / Q000037:antagonists & inhibitors*; D014364:Tryptophan / Q000737:chemistry*
chemical_list: D004151:Dipeptides; D004791:Enzyme Inhibitors; D014364:Tryptophan; D019098:Telomerase