Exploration of certain 1,3-oxazole- and 1,3-thiazole-based hydroxamic acids as histone deacetylase inhibitors and antitumor agents
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- Exploration of certain 1,3-oxazole- and 1,3-thiazole-based hydroxamic acids as histone deacetylase inhibitors and antitumor agents
- D T Anh; P T Hai; L T T Huong; E J Park; H W Jun; Jong Soon Kang; Joo Hee Kwon; D T M Dung; V T Anh; V T M Hue; S B Han; N H Nam
- Bibliographic Citation
- Bioorganic Chemistry, vol. 101, pp. 103988-103988
- Publication Year
- Several novel series of hydroxamic acids bearing 2-benzamidooxazole/thiazole (5a-g, 6a-g) or 2-phenylsulfonamidothiazole (8a-c) were designed and synthesized. The compounds were obtained straightforwards via a two step pathway, starting from commercially available ethyl 2-aminooxazole-4-carboxylate or ethyl 2-aminothiazole-4-carboxylate. Biological evaluation showed that these hydroxamic acids generally exhibited good cytotoxicity against three human cancer cell lines (SW620, colon; PC-3, prostate; NCI-H23, lung cancer), with IC50 values in low micromolar range and comparable to that of SAHA. These compounds also comparably inhibited HDACs with IC50 values in sub-micromolar range (0.010-0.131 μM) and some compounds (e.g 5f, IC50, 0.010 μM) were even more potent than SAHA (IC50, 0.025 μM) in HDAC inhibition. Representative compounds 6a and 8a appeared to arrest the SW620 cell cycle at G2 phase and significantly induced both early and late apoptosis of SW620 colon cancer cells. Docking experiments on HDAC2 and HDAC6 isozymes revealed favorable interactions at the tunnel of the HDAC active site which positively contributed to the inhibitory activity of synthesized compound. The binding affinity predicted by docking program showed good correlation with the experimental IC50 values. This study demonstrates that simple 1,3-oxazole- and 1,3-thiazole-based hydroxamic acids are also promising as antitumor agents and HDAC inhibitors and these results should provide valuable information for further design of more potent HDAC inhibitors and antitumor agents.
- Histone deacetylase (HDAC) inhibitors; Hydroxamic acids; Docking; 1, 3-oxazole; 1, 3-thiazole
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- Ochang Branch Institute > Division of Bioinfrastructure > Laboratory Animal Resource Center > 1. Journal Articles
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