Antimalarial Activity of Biflavonoids from Ochna integerrima

Abstract

IntroductionMalaria is the major parasitic infection in many tropical and subtropical regions, leading to more than one million deaths (principally among African children) out of 400 million cases each year [1] and to major consequent impacts on economic productivity and livelihood [2]. The incidence of malaria is now increasing because of the appearance of multi-drug resistant Plasmodium falcipalum, therefore new and more effective antimalarial drugs are urgently required.Ochna integerrima Merr. (Ochnaceae) is a tree that is widely distributed in Thailand [3], and the bark of O. integerrima Merr. has been used for digestive disorders as a folk medicine in Thailand [4]. In phytochemical studies on O. integerrima Merr, many flavonoids have been isolated [5], [6], [7]. During a screening for antimalarial active sources among Thai plants, it was found that the 80 % EtOH extract from the outer bark of O. integerrima Merr.showed significant anti-malarial activity. The active ingredients in the outer bark were clarified in the present study. Materials and Methods ApparatusOptical rotations were measured on a JASCO polarimeter. 1 H-and 13 C-NMR spectra were determined on a Varian Mercury-300. Mass spectra (MS) were obtained on JEOL MXA-AM505HA and JMS-700 MStation spectrometers. Chromatographic separations were carried out by column chromatography on Wakogel C-200 (75 ± 150 mm, Wako; Osaka, Japan). Preparative reverse phase HPLC was carried out on PEGASIL (250 20 mm i. d., Senshu Co. Ltd.; Tokyo, Japan). Antimalarial Activity of Biflavonoids from Ochna integerrimaChikara AbstractDuring the screening of antimalarial substances, the 80 % EtOH extract from the outer bark of Ochna integerrima Merr. (Ochnaceae) was shown to have a good anti-malarial activity (IC 50 value: 6.5 mg/mL) whereas extracts from the inner barks of O. integerrima showed no antimalarial activity. Biflavanone (1), which had not been found previously from a natural plant source, was isolated as a potent antimalarial active ingredient (IC 50 value: 80 ng/mL) from the extract of the outer barks. The stereoisomer of 1 ( = compound 2) was also isolated from this plant; however, its activity was significantly lower than that of 1. Key wordsAntimalarial´Ochnaceae´Ochna integerrima Merr.´biflavanones Original Paper 611This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. Analytical methodsAnalytical HPLC experiments were performed on an Agilent 1100 series HPLC instrument (Agilent Technologies Japan, Ltd.; Tokyo, Japan) equipped with a column of PEGASIL (250 4.6 mm i. d., Senshu Co. Ltd.; Tokyo, Japan). The solvent system used was a linear gradient of acetonitrile from 30 % to 60 % during 30 minutes in 10 mM phosphoric acid. Flow rate was 1 mL/min. Injection volume was 10 mL for MeOH solution of all the samples. Concentrations of the samples were 10 mg/mL for extracts and 1 mg/ mL for the isolated compounds. Plant material Extraction and isolationThe outer barks of O. integerrima (485 g) were extracted with 80...

Antiplasmodial activity of (I-3,II-3)-biflavonoids and other constituents from Ormocarpum kirkii

“…This indicated that the I-Aring had a hydroxy group at C-7, whereas the II-A-ring had hydroxy groups at C-5 and C-7. The 13 C NMR resonances of the biflavanone were in good agreement with those of chamaejasmin (Niwa et al, 1986) and biliquiritigenin (Ichino et al, 2006). The 2D COSY, HSQC and HMBC experiments confirmed the (I-3,II-3)-connection of the two flavanone units.…”

“…The compounds comprised seven (I-3,II-3)-biflavonoids, three bi-4-phenyldihydrocoumarins, an isoflavanone and a C-glucosylated flavone. The known compounds were identified as (+)-chamaejasmin (7) (Niwa et al, 1986) which was the major constituent of the crude extract, isochamaejasmin (8) (Niwa et al, 1984(Niwa et al, , 1986, (I-3,II-3)-biliquiritigenin (9) (Ichino et al, 2006), ormocarpin (10) (Nyandat et al, 1990), diphysin (11) (Stermitz et al, 1993), and isovitexin (12) (de Moreira et al, 2000). Except for ormocarpin, this is the first report of these components in the Ormocarpum genus.…”

In vitro antimalarial activity of prenylated flavonoids from Erythrina fusca

“…The cytotoxicity of 4 was a little higher than chloroquine (Table 1), and the effect of prenyl substitution on cytotoxicity was not known because the cytotoxicities of the other compounds were not tested. This result postulates that appropriate introduction of prenyl groups into flavonoids, such as the antimalarial biflavanone [3,4], may lead to more useful derivatives for construction of an antimalarial agent.…”

“…Therefore, new and more effective antimalarial drugs are necessary [2]. It has been reported that biflavanones and flavonol glycosides were found to possess antimalarial activity [3][4][5][6]. However, there is no report on free flavonoid as the active substance.…”

Antiplasmodial and leishmanicidal activity of biflavonoids from Indian Selaginella bryopteris

“…Acquired resistance leads to a loss of treatment capacity for currently available drugs (Wellems and Plowe, 2001). Previously, antiprotozoal and antimalarial activity for eight biflavonoids has been reported by Weniger et al (2006) and others (Ichino et al, 2006;Azebaze et al, 2007). The heterosporous fern genus Selaginella is a rich source of biflavonoids (Sun et al, 1997;Silva et al, 1995;Lin et al, 2000;Chen et al, 2005).…”