2. Academic Validation
  3. Novel substituted aminothiazoles as potent and selective anti-hepatocellular carcinoma agents

Novel substituted aminothiazoles as potent and selective anti-hepatocellular carcinoma agents

  • Bioorg Med Chem Lett. 2016 Dec 1;26(23):5819-5824. doi: 10.1016/j.bmcl.2016.10.015.
Huagang Lu 1,  John Rogowskyj 1,  Wenquan Yu 1,  Anu Venkatesh 2,  Noshena Khan 1,  Shigeki Nakagawa 2,  Nicolas Goossens 2,  Anna P Koh 2,  Takaaki Higashi 2,  Ganesh Gunasekaran 3,  Myron E Schwarz 3,  Spiros P Hiotis 4,  Xiaodong Xu 1,  William Kinney 1,  Yujin Hoshida 2,  Timothy Block 1,  Andrea Cuconati 5,  Yanming Du 6
Affiliations

Affiliations

  • 1 Baruch S. Blumberg Institute, 3805 Old Easton Road, Doylestown, PA 18902, United States.
  • 2 Division of Liver Diseases, Department of Medicine, Liver Cancer Program, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, United States.
  • 3 Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, United States.
  • 4 Division of Surgical Oncology, Department of Surgery, Icahn School of Medicine at Mount Sinai, United States.
  • 5 Baruch S. Blumberg Institute, 3805 Old Easton Road, Doylestown, PA 18902, United States. Electronic address: [email protected].
  • 6 Baruch S. Blumberg Institute, 3805 Old Easton Road, Doylestown, PA 18902, United States. Electronic address: [email protected].
PMID: 27793566 DOI: 10.1016/j.bmcl.2016.10.015
Abstract

Based on our previous identification of a disubstituted aminothiazole termed HBF-0079 with promising selective toxicity for HCC-derived cell lines versus non-HCC liver lines, a series of tri-substituted aminothiazole derivatives were prepared and evaluated. This work resulted in the discovery of isopropyl 4-(pyrazin-2-yl)-2-(pyrimidin-2-ylamino)thiazole-5-carboxylate, 14, which displayed EC50 value of 0.11μM and more than 450times of selectivity, and its methyl carbonate prodrug 24 with improved solubility in organic Solvents. Furthermore, 14, was shown to reduce the proliferation of several liver Cancer cells derived directly from patients.

Keywords

Hepatocellular carcinoma (HCC); Prodrug; Substituted aminothiazole.

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