RESUMO
Coumarin molecules are ubiquitous in nature. Several have come to prominence as potential clinical therapeutic candidates. The principal example is warfarin, which is a very widely prescribed anticoagulant. Other coumarin derivatives, such as aflatoxin B1, are insidious contaminants in crop-derived foodstuffs. Extreme potency is a common feature of all biochemically active coumarins and, thus reliable methods for their rapid and sensitive detection are of paramount importance. Accordingly, this review examines the current methods used in the analysis of these molecules and compares them with immunoassay-based strategies. As a case study, we report on our experiences with using coumarin-specific polyclonal, monoclonal, and recombinant antibodies in conjunction with a surface plasmon resonance-based biosensor for analysis of coumarins. We chart the assay development process and demonstrate high sensitivity and reproducibility that compares favorably with established methodologies.
Assuntos
Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/métodos , Técnicas de Química Analítica/métodos , Cumarínicos/análise , Ressonância de Plasmônio de Superfície/métodos , Aflatoxina B1/análise , Animais , Cumarínicos/química , Imunoglobulina G/química , Modelos Químicos , Reprodutibilidade dos Testes , Umbeliferonas/análise , Varfarina/antagonistas & inibidores , Varfarina/farmacologiaRESUMO
The Benzopyrones are a group of compounds whose members include coumarins and flavonoids. Dietary exposure to benzopyrones is quite significant, as these compounds are found in vegetables, fruit, seeds, nuts, coffee, tea and wine. It is estimated that the average western diet contains approximately 1 g/day of mixed benzopyrones. It is, therefore, not difficult to see why extensive research into their pharmacological and therapeutic properties is underway over many years. Coumarin is a natural substance that has shown anti-tumour activity in vivo, with the effect believed to be due to its metabolites (e.g. 7-hydroxycoumarin). This review is based on recent studies of coumarins and coumarin related compounds. Therefore, the focus will be on these relevant compounds and their therapeutic importance. A recent study has shown that 7-hydroxycoumarin inhibits the release of Cyclin D1, which is overexpressed in many types of cancer. This knowledge may lead to its use in cancer therapy. Esculetin inhibits growth and cell cycle progression by inducing arrest of the G(1) phase in HL-60 leukaemia cells, resulting from the inhibition of retinoblastoma protein phosphorylation. Recent studies investigating the potential of flavonoids as therapeutic agents have suggested they may have use in various therapeutic settings ranging from leukaemia treatment to the treatment of patients with HIV. Genistein is a well-known isoflavone and is a tyrosine kinase inhibitor. Studies have indicated that genistein elicits inhibitory effects on cell growth of various carcinoma cell-lines and may be a potential candidate for cancer therapy. In our research, we have investigated the effects of coumarins and coumarin-related compounds on a panel of cell-lines. The most recent work involves two cell-lines, MCF-7 a breast carcinoma and A549 a lung carcinoma. Microtitre assays were performed along with real-time analysis of cell viability using a biosensor called the Cytosensor microphysiometer. These studies suggest that both genistein and esculetin exerted the most potent inhibitory effect on cell growth in comparison to the other two compounds.