Studies on the Chemical Constituents of Stem Bark of Millettia leucantha: Isolation of New Chalcones with Cytotoxic, Anti-herpes Simplex Virus and Anti-inflammatory Activities.

Abstract

The genus Millettia WEIGHT et ARN. (Leguminosae) consists of ca. 100 old world species of climbers and trees, and their seeds and other parts are in some cases known to show insecticidal and piscicidal properties.1) In previous studies 2) flavonoids, isoflavonoids and alkaloids were isolated as chemical components. M. leucantha KURZ is a lofty tree, with pinnate leaves and white flowers, growing throughout Thailand 3); however, its medicinal use is unknown. The present investigation deals with the isolation of chalcone derivatives (1, 2, 4, 6, 7, 10) including four new ones (1, 4, 7, 10) and flavones (3, 5, 8, 9, 11) from the stem bark, and their cytotoxic, antiviral and anti-inflammatory activities. Isolation of Chemical ConstituentsRepeated column chromatography (CC) of the ethanolic extract of the stem bark of M. leucantha afforded eleven products (1-11) in the order of polarity.Among them, seven compounds were identified to be known chalcones, 2Ј-hydroxy-3,4,4Ј,6Ј-tetramethoxychalcone 4,5) (2) and dihydromilletenone methyl ether 6) (6), known furanoflavones, karanjin 7,8) (3) and lanceolatin B 4-6,9) (5), and known simple flavones, desmethoxykanugin 10) (8), 3Ј,4Ј-methylenedioxy-7-methoxyflavone 6) (9), and 3Ј,4Ј-methylenedioxy-5,7-dimethoxyflavone 11) (11), by comparison with reported data. Other chalcone derivatives (1, 4, 7, 10) were found to be new ones. (Chart 1).A new chalcone 1 with molecular formula C 18 H 16 O 5 , was obtained as yellow needles. The 1 H-NMR spectrum (Table 1) showed a set of trans-olefinic protons at d 7.35 and 7.60, a methylenedioxy group at d 6.01 and two methoxy substituents at d 3.87 and 3.91, in addition to two ABX aromatic systems. In electron impact mass spectrum (EI-MS) a relatively abundant fragment peak observed at m/z 165 [2,4-(MeO) 2 C 6 H 3 -CO ϩ , 43%] indicated that two methoxy groups were located on the A ring connected to the ketonic function in a chalcone system. 12) Thus, 1 was determined to be 2Ј,4Ј-dimethoxy-3,4-methylenedioxychalcone, which has been Compound 7, b-methoxychalcone, obtained as pale yellow needles, had molecular formula C 20 H 20 O 7 . The 1 H-NMR spectrum (Table 1) showed an olefinic proton as a singlet at d 6.33 assigned to H-a. Substitution of the ketonic A ring by a methylenedioxy group was deduced by the appearance of peaks at m/z 149 (3,4-OCH 2 O-C 6 H 3 -CO ϩ , 27%) and 121 (3,4-OCH 2 O-C 6 H 3 ϩ , 20%) in EI-MS. Furthermore, a base peak (m/z 341) was reasonably assigned to be a benzopyrilium cation 13,14) produced by the loss of a methoxy group Engineering and Biotechnology; 73/1 Rama VI Road, Rajathevee, Bangkok 10400, Thailand: c Drug Research Department, R&D Division, Nippon Kayaku Co., Ltd.; 3-31-12 Shimo, Kita-ku, Tokyo 115-8588, Japan: and d Graduate School of Pharmaceutical Sciences, Chiba University; 1-33 Yayoi, Inage-ku, Chiba 263-8522, Japan. Received August 16, 2002; accepted November 19, 2002 Four new chalcone derivatives (1, 4, 7, 10) were isolated from the stem bark of Millettia leucantha KURZ (Leguminosae) along wit...

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