2. Academic Validation
  3. Isosteres of ester derived glucose uptake inhibitors

Isosteres of ester derived glucose uptake inhibitors

  • Bioorg Med Chem Lett. 2020 Sep 15;30(18):127406. doi: 10.1016/j.bmcl.2020.127406.
Dennis A Roberts 1,  Liyi Wang 1,  Weihe Zhang 1,  Yi Liu 2,  Pratik Shriwas 3,  Yanrong Qian 4,  Xiaozhuo Chen 5,  Stephen C Bergmeier 6
Affiliations

Affiliations

  • 1 Department of Chemistry and Biochemistry, Ohio University, Athens, OH 45701, USA.
  • 2 Department of Biomedical Science, Ohio University, Athens, OH 45701, USA; Program of Molecular and Cellular Biology, Ohio University, Athens, OH 45701, USA.
  • 3 Program of Molecular and Cellular Biology, Ohio University, Athens, OH 45701, USA.
  • 4 Department of Chemistry and Biochemistry, Ohio University, Athens, OH 45701, USA; Edison Biotechnology Institute, Ohio University, Athens, OH 45701, USA; Program of Molecular and Cellular Biology, Ohio University, Athens, OH 45701, USA.
  • 5 Department of Chemistry and Biochemistry, Ohio University, Athens, OH 45701, USA; Edison Biotechnology Institute, Ohio University, Athens, OH 45701, USA; Department of Biomedical Science, Ohio University, Athens, OH 45701, USA; Program of Molecular and Cellular Biology, Ohio University, Athens, OH 45701, USA.
  • 6 Department of Chemistry and Biochemistry, Ohio University, Athens, OH 45701, USA; Program of Molecular and Cellular Biology, Ohio University, Athens, OH 45701, USA. Electronic address: bergmeis@ohio.edu.
PMID: 32736210 DOI: 10.1016/j.bmcl.2020.127406
Abstract

Glucose transporters (GLUTs) facilitate glucose uptake and are overexpressed in most Cancer cells. Inhibition of glucose transport has been shown to be an effective method to slow the growth of Cancer cells both in vitro and in vivo. We have previously reported on the Anticancer activity of an ester derived glucose uptake inhibitor. Due to the hydrolytic instability of the ester linkage we have prepared a series of isosteres of the ester moiety. Of all of the isosteres prepared, the amine linkage showed the most promise. Several additional analogues of the amine-linked compounds were also prepared to improve the overall activity.

Keywords

Bioisostere; Cancer; GLUT; Glucose uptake; Transporters.

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