Archives of Pharmacal Research

The Pharmaceutical Society of Korea (대한약학회)
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Inhibitory Effects of Furoquinoline Alkaloids from Melicope confusa and Dictamnus albus against Human Phosphodiesterase 5 (hPDE5A) In Vitro

  • Nam Kung-woo (Jung-San Biotechnology Institute, Natural Products Research Institute, Seoul National University, College of Pharmacy) ;
  • Je Kang-Hoon (Natural Products Research Institute, Seoul National University, College of Pharmacy) ;
  • Shin Young-Jun (Jung-San Biotechnology Institute) ;
  • Kang Sam Sik (Natural Products Research Institute, Seoul National University, College of Pharmacy) ;
  • Mar Woongchon (Natural Products Research Institute, Seoul National University, College of Pharmacy)
  • Published : 2005.06.01
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Abstract

Eight furoquinoline alkaloids were purified from two plants belonging to the Rutaceae family. Kokusaginine. skimmianine, evolitrine, and confusameline were purified from Melicope confusa, and haplopine, robustine, dictamine, and $\gamma$-fagarine from Dictamnus albus. In this study, the eight furoquinoline alkaloids were examined for inhibitory potency against human phos-phodiesterase 5 (hPDE5A) in vitro. DNA encoding the catalytic domain of human PDE5A was amplified from the mRNA of T24 cells by RT-PCR and was fused to GST in an expression vector. GST-tagged PDE5A was then purified by glutathione affinity chromatography and used in inhibition assays. Of the eight alkaloids, $\gamma$-fagarine was the most potent inhibitor of PDE5A, and its single methoxy group at the C-8 position was shown to be critical for inhibitory activity. These results clearly illustrate the relationship between PDE5A inhibition and the methoxy group position in furoquinoline alkaloids.

Keywords

References

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