Coumarins and Neoflavones: Synthesis and HCV NS5B Polymerase Inhibition

Coumarins and Neoflavones: Synthesis and HCV NS5B Polymerase Inhibition

Moraes, Paula de F. de; Leão, Raquel A. C.; Nichols, Daniel Brian; Basu, Amartya; Chudayeu, Maksim; Talele, Tanaji T.; Kaushik-Basu, Neerja; Costa, Paulo R. R.

Abstract:

Hepatitis C virus (HCV) is the leading cause of malignant chronic liver disease such as fibrosis, cirrhosis and hepatocellular carcinoma. Some years ago we report on the coumestan family of phytoestrogens as a new class of non-nucleoside HCV NS5B polymerase inhibitor. Wedelolactone and LQB-34 were the most potent (Figure 1). However, further efforts to optimize the coumestan scaffold proved discouraging as the synthesis of new derivatives involved multiple steps and expensive chemicals. We therefore sought to explore a trimmed version of coumestans, such as coumarins and neoflavones, which comprise of a bicyclic scaffold as opposed to a tetracyclic one present in LQB-34, as potential HCV NS5B inhibitors.

Hepatitis C virus (HCV) is the leading cause of malignant chronic liver disease such as fibrosis, cirrhosis and hepatocellular carcinoma. Some years ago we report on the coumestan family of phytoestrogens as a new class of non-nucleoside HCV NS5B polymerase inhibitor. Wedelolactone and LQB-34 were the most potent (Figure 1). However, further efforts to optimize the coumestan scaffold proved discouraging as the synthesis of new derivatives involved multiple steps and expensive chemicals. We therefore sought to explore a trimmed version of coumestans, such as coumarins and neoflavones, which comprise of a bicyclic scaffold as opposed to a tetracyclic one present in LQB-34, as potential HCV NS5B inhibitors.

Palavras-chave:

DOI: 10.5151/chempro-15bmos-BMOS2013_2013818222912

Referências bibliográficas

• [1] 1 Kaushik-Basu, N., e cols., Nucleic Acids Res. 2008, 36, 1482.
• [2] 2 Pocas E.S., e cols., Bioorg Med Chem. 2006, 14, 7962.
• [3] 3 Leão R. A. C., e cols., Synthesis-Stuttgart, 2011, 22, 3692.
• [4] 4 Nichols D. B., e cols., Chem. Biol. Drug Design, 2013, 81, 607.

Como citar:

Moraes, Paula de F. de; Leão, Raquel A. C.; Nichols, Daniel Brian; Basu, Amartya; Chudayeu, Maksim; Talele, Tanaji T.; Kaushik-Basu, Neerja; Costa, Paulo R. R.; "Coumarins and Neoflavones: Synthesis and HCV NS5B Polymerase Inhibition", p-164-164. In: In Blucher Chemistry Proceedings, São Paulo, v. 1, n. 2, Dezembro.2013. São Paulo: Blucher, 2013.
ISSN 23184043, DOI 10.5151/chempro-15bmos-BMOS2013_2013818222912