title: Novel structural motifs consisting of chiral thiazolines: synthesis, molecular recognition, and anticancer activity.
abstract: The facile synthesis of linear and cyclic chiral oligo(4-alpha/beta-methyl)thiazolines is described. Linear oligothiazolines have been efficiently synthesized by the iterative formation of thiazoline rings and two-directional block condensation. The construction of 24- to 36-membered cyclic oligothiazolines was achieved through the head-to-tail cyclo-oligomerization of doubly deprotected linear fragments. Studies of the interactions of both the linear and cyclic oligomers with chiral compounds revealed that cyclic oligomers displayed a strong binding affinity towards mandelic acid, whereas linear oligomers showed a poor affinity. Linear oligomers have been proven to inhibit the cell growth of the cancer cell lines HPAC, PC-3, and HCT-116. Studies of the structure-activity relationships showed that the IC50 values are clearly dependent on both the length and the terminal functionalities of the linear oligomers. Longer derivatives showed more potent activity (e.g., hexi- and octithiazolines exhibit IC50<1 microM) against all three cancer cell lines. In sharp contrast, cyclic oligomers were inactive to all three cell lines.
authors.affiliation: PRESTO, The Japan Science and Technology Agency, Hongo, Tokyo 113-0033, Japan.
authors.forename: Fu She
authors.initials: FS
authors.lastname: Han
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Osajima
authors.forename: Mui
authors.initials: M
authors.lastname: Cheung
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Tokuyama
authors.forename: Tohru
authors.initials: T
authors.lastname: Fukuyama
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002470:Cell Survival; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology; D006801:Humans; D047028:Macrocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D015394:Molecular Structure; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D047028:Macrocyclic Compounds; D013844:Thiazoles