EVALUATION OF FOURTEEN AURONE DERIVATIVES AS POTENTIAL ANTI-CANCER AGENTS

Gheda Alsaif, Nadin Almosnid, Ian Hawkins, Zachary Taylor, Deborah L.T. Knott, Scott Handy, Elliot Altman and Ying Gao

Department of Biology, Middle Tennessee State University, Murfreesboro, USA

Abstract

Background: Aurones are a sub-set of the flavone family that possess a number of biological activities, including anti-cancer, anti-inflammatory, anti-microbial, anti-parasitic and anti-viral. Due to their high availability, simple synthesis, and generally low toxicity, aurones could be attractive candidates for safer cancer drugs. This study aims to evaluate the anti-proliferation and anti-metastasis activity of a series of synthesized aurone derivatives. Methods: A series of aurone derivatives with simple unsubstituted coumaranone (benzofuranone) fragments and a range of alkylidene fragments have been prepared and tested for anti-proliferation activity against human cancer cell lines A549 (lung), BT20 (breast) and MCF7 (breast), and anti-metastasis activity against A549. Results: Several of these compounds displayed significant levels of activity and high levels of selectivity for the inhibition of the growth of cancerous cell lines versus the corresponding normal cell lines. This growth inhibition was found to be associated with the induction of apoptosis in cancer cells. Moreover, several aurone derivatives showed remarkable inhibition on the motility of lung cancer cells A549 at a concentration as low as 6.25 μM. Analysis of the structure-activity relationship revealed that the aurone derivatives based upon five-membered heteroaromatic rings exhibited the most significant anti-cancer activity. Conclusion: Aurone derivatives devoid of the unusual oxygenation found in the coumaranone fragment are potential leads for new anti-cancer agents.

Keywords: Aurones, benzofuranone, anti-cancer, selectivity, apoptosis, cell motility.