title: Screening of promising chemotherapeutic candidates from plants against human adult T-cell leukemia/lymphoma (V): coumarins and alkaloids from Boenninghausenia japonica and Ruta graveolens.
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.
authors.affiliation: Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nakano
authors.affiliation: 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.
authors.forename: Kenji
authors.initials: K
authors.lastname: Ishitsuka
authors.affiliation: Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.
authors.forename: Narumi
authors.initials: N
authors.lastname: Matsuda
authors.affiliation: Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.
authors.forename: Ai
authors.initials: A
authors.lastname: Kouguchi
authors.affiliation: Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Tsuchihashi
authors.affiliation: Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Okawa
authors.affiliation: Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.
authors.forename: Hikaru
authors.initials: H
authors.lastname: Okabe
authors.affiliation: Department of Internal Medicine, Division of Medical Oncology, Hematology and Infectious Disease, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tamura
authors.affiliation: Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan. kinjojun@fukuoka-u.ac.jp.
authors.forename: Junei
authors.initials: J
authors.lastname: Kinjo
mesh_terms: D000470:Alkaloids / Q000737:chemistry*; D003374:Coumarins / Q000737:chemistry*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D011564:Furocoumarins / Q000737:chemistry*; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy*; D010936:Plant Extracts / Q000737:chemistry / Q000627:therapeutic use*; D032105:Ruta / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D000470:Alkaloids; D003374:Coumarins; D004365:Drugs, Chinese Herbal; D011564:Furocoumarins; D010936:Plant Extracts
keywords: Adult T-cell leukemia/lymphoma; Alkaloid; Boenninghausenia japonica; Coumarin; Ruta graveolens; Screening