Title:Evaluation of Multifunctional Hybrid Analogs for Stilbenes, Chalcones and Flavanones
VOLUME: 17 ISSUE: 14
Author(s):Ali Cagir*, Burcu Odaci, Mehmet Varol, Ismail Akcok, Ozgur Okur and Ayse T. Koparal
Affiliation:Department of Chemistry, Faculty of Science, Izmir Institute of Technology, Izmir, Department of Chemistry, Faculty of Science, Izmir Institute of Technology, Izmir, Department of Biology, Faculty of Science, Anadolu University, Eskisehir, Department of Chemistry, Faculty of Science, Izmir Institute of Technology, Izmir, Biotechnology and Bioengineering Research and Application Center, Izmir Institute of Technology, Izmir, Department of Biology, Faculty of Science, Anadolu University, Eskisehir
Keywords:Hybrid molecule, anti-cancer, anti-angiogenic, aromatase inhibition, CYP19, analogs.
Abstract:Aims: In this study, discovery of novel anticancer agents acting by more than one mechanism was
aimed.
Method: For this purpose, eleven previously synthesized simple-stilbene, chalcone, flavanone derivatives and
31 novel stilbene-fused chalcones and stilbene-fused flavanones were tested for their aromatase inhibition, antiangiogenic
and anti-proliferative properties in cancer (PC3, MCF-7) and healthy (HUVEC) cell lines. MTT cell
viability assay was used to evaluate the anti-proliferative activities of the compounds. CYP19/MFC highthroughput
screening kit (BD Biosciences, Oxford, UK) was used to search the aromatase inhibition properties
and matrigel tube formation assay was applied to determine the anti-angiogenic activities.
Results: Results indicate that the simple-chalcone and flavanone derivatives were more cytotoxic than the simple-
stilbenes in the both cancer cell lines. In contrast, the simple-stilbene structures were much more effective at
aromatase inhibition. The cytotoxicity profiles of stilbene-fused chalcones in cancer cells imply that these molecules
mostly mimic the simple chalcone structures. On the other hand, flavanones lose their cytotoxic activities
after becoming fused with stilbenes. Additionally, aromatase inhibition assays showed that stilbene-fused chalcones
again do mimic the simple-chalcones but not simple-stilbenes and anti-angiogenic profiles of the tested
molecules seem to be not related with stilbene fragments. Furthermore, stilbene-fused flavanones may mimic
both simple-flavanones and simple-stilbenes depending upon the type and position of the substituent in their
respective terminal aromatic rings.
