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RRC ID 69454
著者 Iqbal J, Saeed A, Raza R, Matin A, Hameed A, Furtmann N, Lecka J, Sévigny J, Bajorath J.
タイトル Identification of sulfonic acids as efficient ecto-5'-nucleotidase inhibitors.
ジャーナル Eur J Med Chem
Abstract Ecto-5'-nucleotidase (CD73) is well known for its implication in cancer. Inhibition of ecto-5'-nucleotidases is thought to provide an attractive approach to cancer therapy. This study identifies sulfonic acid compounds as efficient inhibitors of ecto-5'-nucleotidases. The compounds were tested against recombinant human and rat ecto-5'-nucleotidases. The most potent new sulfonic acid inhibitor 6-amino-4-hydroxynaphthalene-2-sulfonic acid (1) of ecto-5'-nucleotidase had an IC₅₀ of 1.32 ± 0.09 μM for the human and 10.4 ± 3.3 μM for the rat enzyme. Generally, all compounds were more active against the human enzyme. Plausible binding mode models were developed for this new class of inhibitors. Furthermore, several sulfonic acid inhibitors were efficient cytotoxic agents when tested on H157 cancer cell lines. Hence, new ecto-5'-nucleotidases inhibitors displayed significant potential for further development as compounds for anti-cancer therapy.
巻・号 70
ページ 685-91
公開日 2013-1-1
DOI 10.1016/j.ejmech.2013.10.053
PII S0223-5234(13)00694-6
PMID 24215819
MeSH 5'-Nucleotidase / antagonists & inhibitors* 5'-Nucleotidase / metabolism Animals Antineoplastic Agents / chemical synthesis Antineoplastic Agents / chemistry Antineoplastic Agents / pharmacology* Cell Proliferation / drug effects Cells, Cultured Crystallography, X-Ray Dose-Response Relationship, Drug Drug Screening Assays, Antitumor Enzyme Inhibitors / chemical synthesis Enzyme Inhibitors / chemistry Enzyme Inhibitors / pharmacology* Humans Models, Molecular Molecular Structure Rats Recombinant Proteins / metabolism Structure-Activity Relationship Sulfonic Acids / chemical synthesis Sulfonic Acids / chemistry Sulfonic Acids / pharmacology* Vincristine / pharmacology
IF 5.573
リソース情報
ヒト・動物細胞 HCE-T(RCB2280)