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Compounds obtained fromSida 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

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Abstract

Activity-guided fractionation of the EtOAc-soluble extract of the whole plants ofSida acuta using a bioassay based on the induction of quinone reductase (QR) 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, (±)-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, compounds1-3 and1a exhibited the most potent QR activity, with observed CD (concentration required to double induction) values ranging from 0.01 to 0.12 μg/mL. Six compounds were then evaluated in a mouse mammary organ culture assay, with cryptolepinone (2),N-trans-fer-uloyltyramine (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 μg/mL.

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Authors and Affiliations

  1. Program for Collaborative Research in the Pharmaceutical Sciences and Department of Medicinal Chemistry and Pharmacognosy, Center for Pharmaceutical Biotechnology, College of Pharmacy, University of Illinois at Chicago, 60612, Chicago, IL, U.S.A.

    Dae Sik Jang, Eun Jung Park, Young-Hwa Kang, Bao-Ning Su, James G. Graham, Harry H. S. Fong, John M. Pezzuto & A. Douglas Kinghorn

  2. Department of Surgical Oncology, College of Medicine, University of Illinois at Chicago, 60612, Chicago, IL, U.S.A.

    Michael E. Hawthorne, Fernando Cabieses & Rajendra G. Mehta

  3. Instituto Nacional de Medicina Tradicional (INMETRA), Minesterio de Salud, Jesus Maria, Lima, Peru

    Jose Schunke Vigo

  4. Heine Pharmacy Building, Purdue University, 47907, West Lafayette, Indiana, U.S.A.

    John M. Pezzuto

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  1. Dae Sik Jang
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  2. Eun Jung Park
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  4. Bao-Ning Su
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  9. Harry H. S. Fong
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Correspondence to A. Douglas Kinghorn.

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Jang, D.S., Park, E.J., Kang, YH. et al. Compounds obtained fromSida 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. Arch Pharm Res 26, 585–590 (2003). https://doi.org/10.1007/BF02976704

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