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Updated: Jul 17, 2026

Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
Published on: February 9, 2021
Novel structural motifs consisting of chiral thiazolines: synthesis, molecular recognition, and anticancer activity
Fu She Han1, Hiroyuki Osajima, Mui Cheung
1PRESTO, The Japan Science and Technology Agency, Hongo, Tokyo 113-0033, Japan.
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.
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