Chemical constituents from Melicope pteleifolia leaves and their anti-influenza virus activities

Melicope pteleifolia (Champ. Ex Benth) T.G. Hartley (synonym Euodia lepta (Spreng.) Merr.), belonging to Rutaceae family, is a medium-sized tree, which is widely distributed in South and South-East Asia. In traditional medicine, the extract prepared from M. pteleifolia is empirically used for the treatment of remittent fever, colds and various inflammatory conditions. Previous phytochemical investigations revealed that the main constituents of this plant were benzopyrans [1], furoquinoiline alkaloids [2], and glycosidic compounds [3]. Our ongoing chemical investigation revealed the occurrence of rare spiroketal constitutents from the polar fractions of a methanol extract of M. pteleifolia leaves'. The phytochemical investigation was carried out by employing various chromatographic methods, resulting in the isolation of a total 24 compounds (1-24). On the basis of spectroscopic analyses, including NMR, UV, IR and MS and by spectral comparison with published literature, the isolated compounds were determined as five new acetophenones bearing spiroketal-hexofuranoside rings (1-5), one new C-glycosidic acetophenone (11) and two new benzopyrans (13, 14), together with 16 known compounds. This is also the first report of natural occurrence of spiroketal-hexofuranosides (1-5) from M. pteleifolia leaves. To scientifically clarify the traditional usage of M. pteleifolia leaves for treating fever and colds, all isolated compounds were screened for their inhibitory activities against neuraminidases from four different influenza viral strains (H1N1, H9N2, wild-type H1N1 and oseltamivir-resistant H1N1 with H274Y mutation) [4]. Among them, compound 10 was found to exhibit the strongest inhibition against those types of neuraminidase (IC₅₀= 24.93 ± 3.46, 23.19 ± 5.41, 26.67 ± 5.16 and 40.16 ± 4.50µM, respectively). Furthermore, in the cytopathic effect (CPE) assay, compounds 7, 8 and 10 also showed the reduction of H1N1-induced cytopathic effect in MDCK cells.

Keywords: Melicope pteleifolia, Rutaceae, spiroketal-hexofuranosides, spiroketal, benzopyran, neuraminidase, oseltamivir-resistant, H1N1.

References:

[1] Kamperdick C, Van NH, Van Sung T, Adam G. Benzopyrans from Melicope ptelefolia leaves. Phytochemistry 1997; 45: 1049 – 1056

[2] Sichaem J, Jirasirichote A, Sapasuntikul K, Khumkratok S, Sawasdee P, Do TM, Tip-Pyang S. New furoquinoline alkaloids from the leaves of Evodia lepta. Fitoterapia 2014; 92: 270 – 273

[3] Zhang Y, Yang LJ, Jiang K, Tan CH, Tan JJ, Yang PM, Zhu DY. Glycosidic constituents from the roots and rhizomes of Melicope pteleifolia. Carbohyd Res 2012; 361: 114 – 119

[4] Dao TT, Tung BT, Nguyen PH, Thuong PT, Yoo SS, Kim EH, Kim SK, Oh WK. C-Methylated flavonoids from Cleistocalyx operculatus and their inhibitory effects on novel influenza A (H1N1) neuraminidase. J Nat Prod 2010; 73: 1636 – 1642

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