Evaluation of Multifunctional Hybrid Analogs for Stilbenes, Chalcones and Flavanones

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.

Keywords: CYP19; Hybrid molecule; analogs.; anti-angiogenic; anti-cancer; aromatase inhibition.