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

Sohair L El-Ansary; Mohammed M Hussein; Doaa E Abdel Rahman; Lina M A Abdel Ghany

doi:10.1016/j.bioorg.2014.02.003

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

Bioorg Chem. 2014 Apr:53:50-66. doi: 10.1016/j.bioorg.2014.02.003. Epub 2014 Feb 19.

Authors

Sohair L El-Ansary¹, Mohammed M Hussein¹, Doaa E Abdel Rahman², Lina M A Abdel Ghany³

Affiliations

¹ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo 11562, Egypt; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Misr University for Science and Technology, 6th October City, Egypt.
² Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo 11562, Egypt. Electronic address: doaaezzat2004@yahoo.com.
³ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Misr University for Science and Technology, 6th October City, Egypt.

PMID: 24607350
DOI: 10.1016/j.bioorg.2014.02.003

Abstract

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.

Keywords: Anticancer; Benzopyrones; Casein kinase II; Docking studies.

MeSH terms

Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Benzoxazines / chemical synthesis
Benzoxazines / chemistry
Benzoxazines / pharmacology
Binding Sites
Casein Kinase II / antagonists & inhibitors*
Casein Kinase II / metabolism
Cell Line, Tumor
Cell Proliferation / drug effects
Cell Survival / drug effects
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

Substances

Antineoplastic Agents
Benzoxazines
Protein Kinase Inhibitors
Pyrones
Casein Kinase II