Chemical Constituents and Anti-tubercular Activity from the Unripe Pulp of Persea americana

• Main Authors: Ying-Chen Lu, 盧盈辰
• Other Authors: Ih-Sheng Chen
• Format: Others
• Language: zh-TW
• Published: 2011
• Online Access: http://ndltd.ncl.edu.tw/handle/60759555838546166920

碩士 === 高雄醫學大學 === 天然藥物研究所 === 99 === Persea americana Mill. (Lauraceae) is an evergreen tree, distributed in tropical and subtropical regions around the world. Until now, the bark, leaves, fruits and seeds of P. americana have been extensively studied. Previous studies on this plant identified various classes of chemical constituents, such as monoterpenoids, sesquiterpenoids, triterpenoids, flavonoids, steroids, and carotenoids, and especially long-chain fatty alcohol derivatives. From the previous investigations, this plant showed numerous bioactivities, including cytotoxicity, antifungal, antibacterial, acetyl-CoA carboxylase inhibition, nitric oxide and superoxide generation inhibition, and liver injury suppressing effects. Approximately 1300 species of Formosan plants have been screened for antitubercular activity against Mycobacterium tuberculosis H37Rv in vitro, and the methanolic extract of the unripe pulp of P. americana was shown with antitubercular activity. The aims of this study are the isolation of chemical constituents and their antitubercular activity. The methanolic extract of the unripe pulp of P. americana was partitioned into ethyl acetate and water-soluble layers. Bioassay-guided fractionation of the active ethyl acetate-soluble layer has led to the isolation of four new aliphatic alcohols: avocadenols A-D (1-4), avocadoin (5), and eight compounds with acetonide moiety: (2R,4S)-2,4-acetonide- 16-heptadecene-1,2,4-triol (6), (2R,4S,6E)-2,4-acetonide-6-en-16-heptadecene-1,2,4- triol (7), (2R,4S)-2,4-acetonide-16-heptadecyne-1,2,4-triol (8), (2R,4S,6E)-2,4- acetonide-heptadec-6-en-16-yne-1,2,4-triol (9), (2S,4S)-1,2-acetonide-16- heptadecene-1,2,4-triol (10), (2S,4S,6E)-1,2-acetonide-heptadec-6,16-diene-1,2,4- triol (11), (2S,4S)-1,2-acetonide-16-heptadecyne-1,2,4-triol (12) and (2S,4S,6E)-1,2- acetonide-heptadec-6-en-16-yne-1,2,4-triol (13) together with twelve known compounds: oleic acid (14), cedrelopsin (15), (2R,4R)-1-acetoxy-2,4- dihydroxyheptadec-16-ene (22), (2R,4R)-1- acetoxy-2,4-dihydroxyheptadec-16-yne (23), (2R,4R)-1,2,4-trihydroxyheptadec-16-ene (24), (2R,4R)-1,2,4-trihydroxyheptadec- 16-yne (25), 1,4-diacetoxy-2-hydroxyheptadec-16-ene (30), (2R,4R)-1,2,4- trihydroxynonadecane (53), (2R,4R,6E)-1,2,4-trihydroxynonadec-6-ene (54), scopoletin (77), mixtures of β-sitosterol (125) and stigmasterol (126). According to the biosynthesis pathway, we could presume that 6-13 are artificial products produced during purification. The structures of these isolates were elucidated by spectroscopic analysis. Avocadenols A-B (1-2), (2R,4S)-2,4-acetonide-16-heptadecene-1,2,4-triol (6), (2R,4R)-1,2,4-trihydroxynonadecane (53), (2R,4R)-1,2,4-trihydroxyheptadec-16-ene (24), and (2R,4R)-1,2,4-trihydroxyheptadec-16-yne (25) showed antitubercular activity against M. tuberculosis H37Rv in vitro with MIC values of 24.0, 33.8, 50.0, 24.9, and 35.7 μg/mL, respectively.