Discovery of a nanomolar inhibitor of lung adenocarcinoma in vitro

• Published in: Bioorganic & medicinal chemistry letters Vol. 24; no. 21; pp. 5107 - 5110
• Main Authors: Shelton, Jadd R., Balzarini, Jan, Peterson, Matt A.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-11-2014
• Subjects: Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Adenocarcinoma of Lung; Adenosine - analogs & derivatives; Adenosine - pharmacology; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antiproliferative nucleosides; Binding Sites; Bio-active adenosine derivatives; 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 adenocarcinoma; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Molecular Docking Simulation; Purine nucleosides; Structure-Activity Relationship; Antiproliferative nucleosides; Purine nucleosides; Bio-active adenosine derivatives; Lung adenocarcinoma
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2014.08.044

Efficient methods for the preparation of 5′-substituted 5′-amino-5′-deoxy-N6-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=9.7nM).