title: Discovery of a nanomolar inhibitor of lung adenocarcinoma in vitro.
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).
authors.affiliation: Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602, United States.
authors.forename: Jadd R
authors.initials: JR
authors.lastname: Shelton
authors.affiliation: Rega Institute for Medical Research, KU Leuven, B-3000 Leuven, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.affiliation: Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602, United States.
authors.forename: Matt A
authors.initials: MA
authors.lastname: Peterson
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000737:chemistry / Q000378:metabolism; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D062105:Molecular Docking Simulation; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; C498214:BMPR1B protein, human; D052005:Bone Morphogenetic Protein Receptors, Type I; D000241:Adenosine
keywords: Antiproliferative nucleosides; Bio-active adenosine derivatives; Lung adenocarcinoma; Purine nucleosides