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Novel Structural Motifs Consisting of Chiral Thiazolines: Synthesis, Molecular Recognition, and Anticancer Activity
Author(s) -
Han Fu She,
Osajima Hiroyuki,
Cheung Mui,
Tokuyama Hidetoshi,
Fukuyama Tohru
Publication year - 2007
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200601446
Subject(s) - chemistry , computational biology , combinatorial chemistry , stereochemistry , biology
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 IC 50 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 IC 50 <1 μ M ) against all three cancer cell lines. In sharp contrast, cyclic oligomers were inactive to all three cell lines.