Novel structural motifs consisting of chiral thiazolines: Synthesis, molecular recognition, and anticancer activity

Fu She Han, Hiroyuki Osajima, Mui Cheung, Hidetoshi Tokuyama, Tohru Fukuyama

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)

Abstract

The facile synthesis of linear and cyclic chiral oligo(4-α/β- 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 μM) against all three cancer cell lines. In sharp contrast, cyclic oligomers were inactive to all three cell lines.

Original languageEnglish
Pages (from-to)3026-3038
Number of pages13
JournalChemistry - A European Journal
Volume13
Issue number11
DOIs
Publication statusPublished - 2007

Keywords

  • Anticancer agents
  • Macrocycles
  • Molecular recognition
  • Oligomerization
  • Thiazolines

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry

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