For decades, drug resistance has been the major obstacle in the fight against malaria, and the search for new drugs together with the combination therapy constitutes the major approach in responding to this situation. The present study aims at assessing the in vitro antimalarial activity of four compounds isolated from Kigelia africana stem bark (atranorin - KAE1, specicoside - KAE7, 2β,3β,19α-trihydroxy-urs-12-20-en-28-oic acid - KAE3, and p-hydroxy-cinnamic acid - KAE10) and their drug interactions among themselves and their combination effects with quinine and artemether. The antiplasmodial activity and drug interactions were evaluated against the multidrug-resistant W2mef strain of Plasmodium falciparum using the parasite lactate dehydrogenase assay. Three of the four compounds tested were significantly active against W2mef: specicoside (IC(50) = 1.02 ± 0.17 μM), 2β,3β,19α-trihydroxy-urs-12-en-28-oic acid (IC(50) = 1.86 ± 0.15 μM) and atranorin (IC(50) = 1.78 ± 0.18 μM), whereas p-hydroxy-cinnamic acid showed a weak activity (IC(50) = 12.89 ± 0.87 μM). A slight synergistic effect was observed between atranorin and 2β,3β,19α-trihydroxy-urs-12-en-28-oic acid (Combination index, CI = 0.82) whereas the interaction between specicoside and p-hydroxy-cinnamic acid were instead antagonistic (CI = 2.67). All the three compounds showed synergistic effects with artemether, unlike the slight antagonistic interactions of atranorin and 2β,3β,19α-trihydroxy-urs-12-en-28-oic acid in combination with quinine. K. africana compounds are therefore likely to serve as leads in the development of new partner drugs in artemether-based combination therapy.
"In spite of considerable control efforts in many countries , malaria remains a major cause of global morbidity and mortality with substantial global public health costs and with most of the burden in sub-Saharan Africa (Greenwood et al. 2005; Muller 2011). Resistance to the majority of available antimalarial drugs has been reported in a growing number of countries worldwide, and such resistance threatens future progress in malaria control (WHO 2012; Zofou et al. 2012). WHO recommended treating uncomplicated Plasmodium falciparum malaria with artemisinin-based combination therapy (ACT) in order to reduce the risk of resistance. "
[Show abstract][Hide abstract] ABSTRACT: Malaria is an overwhelming impact in the poorest countries in the world due to their prevalence, virulence and drug resistance ability. Currently, there is inadequate armoury of drugs for the treatment of malaria. This underscores the continuing need for the discovery and development of new effective and safe antimalarial drugs. To evaluate the in vitro and in vivo antimalarial activity of the leaf ethyl acetate extract of Murraya koenigii, bioassay-guided chromatographic fractionation was employed for the isolation and purification of antimalarial compounds. The in vitro antimalarial activity was assayed by the erythrocytic stages of chloroquine-sensitive strain of Plasmodium falciparum (3D7) in culture using the fluorescence-based SYBR Green I assay. The in vivo assay was done by administering mice infected with Plasmodium berghei (NK65) four consecutive daily doses of the extracts through oral route following Peter's 4-day curative standard test. The percentage suppression of parasitaemia was calculated for each dose level by comparing the parasitaemia in untreated control with those of treated mice. Cytotoxicity was determined against HeLa cells using MTT assay. Histopathology was studied in kidney, liver and spleen of isolated compound-treated Swiss albino mice. The leaf crude ethyl acetate extract of M. koenigii showed good in vitro antiplasmodial activity against P. falciparum. The in vivo test of the leaf crude ethyl acetate extract (600 mg/kg) showed reduced malaria parasitaemia by 86.6 % against P. berghei in mice. Bioassay-guided fractionation of the leaf ethyl acetate extract of M. koenigii led to the isolation of two purified fractions C3B2 (2.84 g) and C3B4 (1.97 g). The purified fractions C3B2 and C3B4 were found to be active with IC50 values of 10.5 ± 0.8 and 8.25 ± 0.2 μg/mL against P. falciparum, and in vivo activity significantly reduced parasitaemia by 82.6 and 88.2 % at 100 mg/kg/body weight on day 4 against P. berghei, respectively. The isolated fractions C3B2 and C3B4 were monitored by thin-layer chromatography until a single spot was obtained with R f values of 0.36 and 0.52, respectively. The pure compounds obtained in the present investigation were subjected to UV-visible spectroscopy, Fourier transformer infrared spectroscopy, 1D and 2D (1)H-Nuclear magnetic resonance (NMR), (13)C NMR, DEPT, COSY and Mass spectral analysis. Based on the spectral analysis, it is concluded that the isolated compounds were myristic acid (C3B2) and β-caryophyllene (C3B4). The cytotoxic effect of myristic acid and β-caryophyllene showed the TC50 values of >100 and 80.5 μg/mL, respectively against HeLa cell line. The histopathology study showed that protection against nephrotoxicity of kidney, hepatic damage of liver and splenocytes protection in spleen was achieved with the highest dose tested at 100 mg/kg/body weight. The present study provides evidence of antiplasmodial compounds from M. koenigii and is reported for the first time.
Parasitology Research 03/2014; 113(5). DOI:10.1007/s00436-014-3810-3 · 2.10 Impact Factor
"More excitingly, none of these four compounds showed any significant sign of toxicity against the monkey kidney cell strains LLC-MK2 (selectivity index below 10). Compound 39 exhibited antiplasmodial activitity against the W2mef strain with an IC50 value of 2.11 μg mL−1. The origins of the isolated anti-malarial/antiplasmodial phenolics are shown in Table 2, while the chemical structures are shown in Figure 4. "
[Show abstract][Hide abstract] ABSTRACT: Malaria is currently a public health concern in many countries in the world due to various factors which are not yet under check. Drug discovery projects targeting malaria often resort to natural sources in the search for lead compounds. A survey of the literature has led to a summary of the major findings regarding plant-derived compounds from African flora, which have shown anti-malarial/antiplasmodial activities, tested by in vitro and in vivo assays. Considerations have been given to compounds with activities ranging from "very active" to "weakly active", leading to >500 chemical structures, mainly alkaloids, terpenoids, flavonoids, coumarins, phenolics, polyacetylates, xanthones, quinones, steroids and lignans. However, only the compounds that showed anti-malarial activity, from "very active" to "moderately active", are discussed in this review.
"Mbah et al. isolated 3-O-betulinic acid p-coumarate (167) from Baillonella toxisperma, with an IC50 of 1.65 μM . The triterpenoid 2β,3β,19α-trihydroxy-urs-12-20-en-28-oic acid (168) was isolated by Zofou et al.  from the stem bark of Kigelia africana (Bignoniaceae). This compound exhibited an IC50 of 0.90 μg mL-1 against the W2 strain of P. falciparum. "
[Show abstract][Hide abstract] ABSTRACT: Traditional medicine caters for about 80% of the health care needs of many rural populations around the world, especially in developing countries. In addition, plant-derived compounds have played key roles in drug discovery. Malaria is currently a public health concern in many countries in the world due to factors such as chemotherapy faced by resistance, poor hygienic conditions, poorly managed vector control programmes and no approved vaccines. In this review, an attempt has been made to assess the value of African medicinal plants for drug discovery by discussing the anti-malarial virtue of the derived phytochemicals that have been tested by in vitro and in vivo assays. This survey was focused on pure compounds derived from African flora which have exhibited anti-malarial properties with activities ranging from "very active" to "weakly active". However, only the compounds which showed anti-malarial activities from "very active" to "moderately active" are discussed in this review. The activity of 278 compounds, mainly alkaloids, terpenoids, flavonoids, coumarines, phenolics, polyacetylates, xanthones, quinones, steroids, and lignans have been discussed. The first part of this review series covers the activity of 171 compounds belonging to the alkaloid and terpenoid classes.. Data available in the literature indicated that African flora hold an enormous potential for the development of phytomedicines for malaria.
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