Synthesis, docking and in vitro anticancer evaluation of some new benzopyrone derivatives

• Published in: Bioorganic chemistry 2014-04, Vol.53, p.50-66
• Main Authors: El-Ansary, Sohair L., Hussein, Mohammed M., Abdel Rahman, Doaa E., Abdel Ghany, Lina M.A.
• Format: Article
• Language: English
• Subjects: Anticancer; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Benzopyrones; Benzoxazines - chemical synthesis; Benzoxazines - chemistry; Benzoxazines - pharmacology; Binding Sites; Casein kinase II; Casein Kinase II - antagonists & inhibitors; Casein Kinase II - metabolism; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Docking studies; Drug Screening Assays, Antitumor; Humans; Molecular Docking Simulation; Protein Kinase Inhibitors - chemical synthesis; Protein Kinase Inhibitors - chemistry; Protein Kinase Inhibitors - pharmacology; Protein Structure, Tertiary; Pyrones - chemical synthesis; Pyrones - chemistry; Pyrones - pharmacology; Structure-Activity Relationship
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2014.02.003

[Display omitted] •New benzopyrone derivatives were synthesized and characterized.•Compounds were evaluated by NCI, Bethesda for their in vitro anticancer activity.•Most compounds shared binding interactions with CK2 similar to inhibitor DBC. The synthesis of some new 3-alkyl-7-hydroxy-4-methyl-8-substituted-1H-benzopyran-2-ones, 6-alkyl-7-methyl-2-substituted amino-5H-pyrano[6,5-e] benzoxazol-5-ones, 7-alkyl-8-methyl-3-substituted-2,6-dihydropyrano[6,5-f]-1,4-benzoxazin-6-ones, 7,8-disubstituted-3-ethyl-4-methyl-1H-benzopyran-2-ones and 3-alkyl-4-methyl-7-substituted-1H-benzopyran-2-ones were described. Fourteen compounds were selected by National Cancer Institute (NCI), Bethesda, and evaluated for their in vitro anticancer activity in the full NCI 60 cell lines panel assay by a single dose test. Compounds 4a, 18a, 18b and 23a were found to be broad-spectrum antitumors showing effectiveness toward numerous cell lines that belong to different tumor subpanels. Furthermore, docking studies were undertaken to gain insight into the possible binding mode of these compounds with the binding site of the casein kinase II (CK2) enzyme which is involved in cell survival and proliferation through a number of downstream effectors.