Discovery of a nanomolar inhibitor of lung adenocarcinoma in vitro

Jadd R Shelton; Jan Balzarini; Matt A Peterson

doi:10.1016/j.bmcl.2014.08.044

Discovery of a nanomolar inhibitor of lung adenocarcinoma in vitro

Bioorg Med Chem Lett. 2014 Nov 1;24(21):5107-10. doi: 10.1016/j.bmcl.2014.08.044. Epub 2014 Sep 3.

Authors

Jadd R Shelton¹, Jan Balzarini², Matt A Peterson¹

Affiliations

¹ Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602, United States.
² Rega Institute for Medical Research, KU Leuven, B-3000 Leuven, Belgium.

PMID: 25262542
DOI: 10.1016/j.bmcl.2014.08.044

Abstract

Efficient methods for the preparation of 5'-substituted 5'-amino-5'-deoxy-N(6)-ureidoadenosine derivatives are described. Compounds were screened for antiproliferative activity against a panel of murine and human cell lines (L1210, CEM, and HeLa) and/or against the NCI-60. The most potent derivative inhibited the lung adenocarcinoma cell line NCI-H522 at low nanomolar concentrations (GI50 = 9.7 nM).

Keywords: Antiproliferative nucleosides; Bio-active adenosine derivatives; Lung adenocarcinoma; Purine nucleosides.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma / metabolism
Adenocarcinoma / pathology
Adenocarcinoma of Lung
Adenosine / analogs & derivatives*
Adenosine / pharmacology
Antineoplastic Agents / chemistry*
Antineoplastic Agents / pharmacology
Binding Sites
Bone Morphogenetic Protein Receptors, Type I / chemistry
Bone Morphogenetic Protein Receptors, Type I / metabolism
Catalytic Domain
Cell Line, Tumor
Cell Proliferation / drug effects
Cell Survival / drug effects
Drug Evaluation, Preclinical
Drug Screening Assays, Antitumor
HeLa Cells
Humans
Lung Neoplasms / metabolism
Lung Neoplasms / pathology
Molecular Docking Simulation
Structure-Activity Relationship

Substances

Antineoplastic Agents
BMPR1B protein, human
Bone Morphogenetic Protein Receptors, Type I
Adenosine