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Comparative in vivo evaluation of polyalkoxy substituted 4H-chromenes and oxa-podophyllotoxins as microtubule destabilizing agents in the phenotypic sea urchin embryo assay
Affiliation:1. Critical Care, Hospital Universitario de Burgos, Avenida Islas Baleares s/n, 09006 Burgos, Spain;2. Internal Medicine and Infectious Diseases, Hospital Universitario de Burgos, Avenida Islas Baleares s/n, 09006 Burgos, Spain;3. Pediatrics, BioCruces Bizkaia Health Research Institute, Hospital Universitario Cruces, University of the Basque Country UPV/EHU, Barakaldo, Avenida Islas Baleares s/n, 09006 Burgos, Spain;4. Neurosurgery, Hospital Universitario de Burgos, Avenida Islas Baleares s/n, 09006 Burgos, Spain;5. Internal Medicine, Autoinmune Systemic Disorders Unit, Hospital Universitario de Burgos, Avenida Islas Baleares s/n, 09006 Burgos, Spain;6. Pneumology Department, Hospital Universitario de Burgos, Avenida ISlas Baleares s/n, 09006 Burgos, Spain;7. Pharrmacy Department, Hospital Universitario de Burgos, Avenida Islas Baleares s/n, 09006 Burgos, Spain;8. Oncohematologist Department, Hospital Universitario de Burgos, Avenida Islas Baleares s/n, 09006 Burgos, Spain
Abstract:A series of polyalkoxy substituted 7-hydroxy- and 7-methoxy-4-aryl-4H-chromenes were evaluated using the sea urchin embryo model to yield several compounds exhibiting potent antimitotic microtubule destabilizing activity. Data obtained by the assay were further confirmed in the NCI60 human cancer cell screen. The replacement of methylenedioxy ring A and lactone ring D in podophyllotoxin analogues by 7-methoxy, 2-NH2, and 3-CN groups in 4-aryl-4H-chromenes resulted in potent antimitotic microtubule destabilizing agents. Feasible synthesis and high yields render 7-methoxy-4H-chromenes to be a promising series for further anticancer drug development.
Keywords:Oxa-podophyllotoxins  Microtubule destabilizing agents  Sea urchin embryo  Cytotoxicity
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