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Screening of promising chemotherapeutic candidates from plants against human adult T-cell leukemia/lymphoma (V): coumarins and alkaloids from Boenninghausenia japonica and Ruta graveolens

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Abstract

During the course of our studies towards the identification of promising chemotherapeutic candidates from plants against two human T-cell lymphotropic virus type I-infected T-cell lines (MT-1 and MT-2), we screened 17 extracts from 9 rutaceous plants against MT-1 and MT-2 cells. The extracts from the aerial parts and roots of Boenninghausenia japonica, as well as the leaves and roots of Ruta graveolens showed potent antiproliferative effects. After activity-guided fractionation, we isolated 44 compounds from two rutaceous plants, including three new compounds (1–3), which were classified into 26 coumarin analogs (13 coumarins, 8 furanocoumarins, 4 dihydrofuranocoumarins and one dihydropyranocoumarin), 15 alkaloid analogs (7 quinolone alkaloids, 4 acridone alkaloids, 3 furanoquinoline alkaloids and one tetrahydroacridone alkaloid) and 3 flavonoid glycosides. Structure–activity relationship studies were also evaluated. The coumarin compounds (2, 3 and 7–9) bearing a 3-dimethylallyl moiety showed potent activity. Similarly, of all the furanocoumarins evaluated in the current study, compound 17 bearing a 3-dimethylallyl group also showed potent activity. A dihydrofuranocoumarin (27) bearing a 3-dimethylallyl moiety showed the most potent activity. Following 27, compound 28 showed potent activity. These results therefore suggested that the presence of a 3-dimethylallyl moiety was important to the antiproliferative activity of these coumarin analogs.

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Authors and Affiliations

  1. Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan

    Daisuke Nakano, Narumi Matsuda, Ai Kouguchi, Ryota Tsuchihashi, Masafumi Okawa, Hikaru Okabe & Junei Kinjo

  2. Division of Hematology and Immunology Center for Chronic Viral Diseases Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 891-0175, Japan

    Kenji Ishitsuka

  3. Department of Internal Medicine, Division of Medical Oncology, Hematology and Infectious Disease, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan

    Kazuo Tamura

Authors
  1. Daisuke Nakano
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  2. Kenji Ishitsuka
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  3. Narumi Matsuda
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  4. Ai Kouguchi
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  8. Kazuo Tamura
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  9. Junei Kinjo
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Correspondence to Junei Kinjo.

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Nakano, D., Ishitsuka, K., Matsuda, N. et al. Screening of promising chemotherapeutic candidates from plants against human adult T-cell leukemia/lymphoma (V): coumarins and alkaloids from Boenninghausenia japonica and Ruta graveolens . J Nat Med 71, 170–180 (2017). https://doi.org/10.1007/s11418-016-1046-5

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  • DOI: https://doi.org/10.1007/s11418-016-1046-5

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