Six New Phenylpropanoid Derivatives from Chemically Converted Extract of <i>Alpinia galanga</i> (L.) and Their Antiparasitic Activities

• Main Authors: Melanny Ika Sulistyowaty, Nguyen Hoang Uyen, Keisuke Suganuma, Ben-Yeddy Abel Chitama, Kazuhide Yahata, Osamu Kaneko, Sachiko Sugimoto, Yoshi Yamano, Susumu Kawakami, Hideaki Otsuka, Katsuyoshi Matsunami
• Format: Article
• Language: English
• Published: MDPI AG 2021-03-01
• Series: Molecules
• Subjects: <i>Alpinia galanga</i>; <i>Leishmania</i>; <i>Trypanosoma</i>; Plasmodium; chemically converted extract; unnatural natural product
• Online Access: https://www.mdpi.com/1420-3049/26/6/1756
• ISSN: 1420-3049

Chemical conversion of the extract of natural resources is a very attractive way to expand the chemical space to discover bioactive compounds. In order to search for new medicines to treat parasitic diseases that cause high morbidity and mortality in affected countries in the world, the ethyl acetate extract from the rhizome of <i>Alpinia galanga</i> (L.) has been chemically converted by epoxidation using dioxirane generated in situ. The biological activity of chemically converted extract (CCE) of <i>A. galanga</i> (L.) significantly increased the activity against <i>Leishmania major</i> up to 82.6 ± 6.2 % at 25 μg/mL (whereas 2.7 ± 0.8% for the original extract). By bioassay-guided fractionation, new phenylpropanoids (<b>1</b>–<b>6</b>) and four known compounds, hydroquinone (<b>7</b>), 4-hydroxy(4-hydroxyphenyl)methoxy)benzaldehyde (<b>8</b>), isocoumarin <i>cis</i> 4-hydroxymelein (<b>9</b>), and (2<i>S</i>,3<i>S</i>,6<i>R</i>,7<i>R</i>,9<i>S</i>,10<i>S)-</i>humulene triepoxide (<b>10</b>) were isolated from CCE. The structures of isolated compounds were determined by spectroscopic analyses of 1D and 2D NMR, IR, and MS spectra. The most active compound was hydroquinone (<b>7</b>) with IC₅₀ = 0.37 ± 1.37 μg/mL as a substantial active principle of CCE. In addition, the new phenylpropanoid <b>2</b> (IC₅₀ = 27.8 ± 0.34 μg/mL) also showed significant activity against <i>L. major</i> compared to the positive control miltefosine (IC₅₀ = 7.47 ± 0.3 μg/mL). The activities of the isolated compounds were also evaluated against <i>Plasmodium falciparum</i>, <i>Trypanosoma bruce</i>i <i>gambisense</i> and <i>Trypanosoma bruce</i>i <i>rhodeisense.</i> Interestingly, compound <b>2</b> was selectively active against trypanosomes with potent activity. To the best of our knowledge, this is the first report on the bioactive “unnatural” natural products from the crude extract of <i>A. galanga</i> (L.) by chemical conversion and on its activities against causal pathogens of leishmaniasis, trypanosomiasis, and malaria.