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The Pharmaceutical Society of Korea (대한약학회)
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Compounds Obtained from Sida acuta with the Potential to Induce Quinone Reductase and to Inhibit 7,12-Dimethylbenz-[a]anthracene-Induced Preneoplastic Lesions in a Mouse Mammary Organ Culture Model

  • Jang, Dae-Sik (Program for Collaborative Research in the Pharmaceutical Sciences and Department of Medicinal Chemistry and Pharmacognosy, and Center for Pharmaceutical Biotechnology, College of Pharmacy, University of Illinois at Chicago) ;
  • Park, Eun-Jung (Program for Collaborative Research in the Pharmaceutical Sciences and Department of Medicinal Chemistry and Pharmacognosy, and Center for Pharmaceutical Biotechnology, College of Pharmacy, University of Illinois at Chicago) ;
  • Kang, Young-Hwa (Program for Collaborative Research in the Pharmaceutical Sciences and Department of Medicinal Chemistry and Pharmacognosy, and Center for Pharmaceutical Biotechnology, College of Pharmacy, University of Illinois at Chicago) ;
  • Su, Bao-Ning (Program for Collaborative Research in the Pharmaceutical Sciences and Department of Medicinal Chemistry and Pharmacognosy, and Center for Pharmaceutical Biotechnology, College of Pharmacy, University of Illinois at Chicago) ;
  • Hawthorne, Michael-E. (Department of Surgical Oncology, College of Medicine, University of Illinois at Chicago) ;
  • Vigo, Jose-Schunke (Instituto Nacional de Medicina Tradicional (INMETRA), Minesterio de Salud, Jesus Maria, Lima, Peru, Purdue University) ;
  • Graham, James-G. (Program for Collaborative Research in the Pharmaceutical Sciences and Department of Medicinal Chemistry and Pharmacognosy, and Center for Pharmaceutical Biotechnology, College of Pharmacy, University of Illinois at Chicago) ;
  • Cabieses, Fernando (Department of Surgical Oncology, College of Medicine, University of Illinois at Chicago) ;
  • Fong, Harry H.S. (Program for Collaborative Research in the Pharmaceutical Sciences and Department of Medicinal Chemistry and Pharmacognosy, and Center for Pharmaceutical Biotechnology, College of Pharmacy, University of Illinois at Chicago) ;
  • Mehta, Rajendra-G. (Department of Surgical Oncology, College of Medicine, University of Illinois) ;
  • Pezzuto, John-M. (Program for Collaborative Research in the Pharmaceutical Sciences and Department of Medicinal Chemistry and Pharmacognosy, and Center for Pharmaceutical Biotechnology, College of Pharmacy, University of Illinois at Chicago, Heine Pharmach Building, Purdue University) ;
  • Kinghorn, A.-Douglas (Program for Collaborative Research in the Pharmaceutical Sciences and Department of Medicinal Chemistry and Pharmacognosy, and Center for Pharmaceutical Biotechnology, College of Pharmacy, University of Illinois at Chicago)
  • Published : 2003.08.01
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Abstract

Activity-guided fractionation of the EtOAc-soluble extract of the whole plants of Sida acuta using a bioassay based on the induction of quinone reductase (OR) in cultured Hepa 1c1c7 mouse hepatoma cells, led to the isolation of ten active compounds of previously known structure, quindolinone (1), cryptolepinone (2), 11-methoxyquindoline (3), N-trans-feruloyltyramine (4), vomifoliol (5), loliolide (6), 4-ketopinoresinol (7), scopoletin (8), evofolin-A (9), and evofolin-B (10), along with five inactive compounds of known structure, ferulic acid, sinapic acid, syringic acid, ($\pm$)-syringaresinol, and vanillic acid. These isolates were identified by physical and spectral data measurement. A new derivative of quindolinone, 5,10-dimethylquindolin-11-one (1a) was synthesized and characterized spectroscopically. Of the active substances, compounds 1-3 and 1a exhibited the most potent QR activity, with observed CD (concentration required to double induction) values ranging from 0.01 to 0.12 $\mu$ g/mL. Six compounds were then evaluated in a mouse mammary organ culture assay, with cryptolepinone (2), N-trans-feruloyltyramine (4), and 5,10-dimethylquindolin-11-one (1a) found to exhibit 83.3, 75.0, and 66.7% inhibition of 7,12-dimethylbenz[a]anthracene-induced preneoplastic lesions, respectively, at a dose of 10 $\mu\textrm{g}$/mL.

Keywords

References

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