Antiplasmodial and cytotoxic activities of the constituents of Turraea robusta and Turraea nilotica

Abstract

Ethnopharmacological relevanceTurraea robusta and Turraea nilotica are African medicinal plants used for the treatment of a wide variety of diseases, including malaria. The genus Turraea is rich in limonoids and other triterpenoids known to possess various biological activities.Materials and methodsFrom the stem bark of T. robusta six compounds, and from various parts of T. nilotica eleven compounds were isolated by the use of a combination of chromatographic techniques. The structures of the isolated compounds were elucidated using NMR and MS, whilst the relative configuration of one of the isolated compounds, toonapubesin F, was established by X-ray crystallography. The antiplasmodial activities of the crude extracts and the isolated constituents against the D6 and W2 strains of Plasmodium falciparum were determined using the semiautomated micro dilution technique that measures the ability of the extracts to inhibit the incorporation of (G-3H, where G is guanine) hypoxanthine into the malaria parasite. The cytotoxicity of the crude extracts and their isolated constituents was evaluated against the mammalian cell lines African monkey kidney (vero), mouse breast cancer (4T1) and human larynx carcinoma (HEp2).ResultsThe extracts showed good to moderate antiplasmodial activities, where the extract of the stem bark of T. robusta was also cytotoxic against the 4T1 and the HEp2 cells (IC50<10 μg/ml). The compounds isolated from these extracts were characterized as limonoids, protolimonoids and phytosterol glucosides. These compounds showed good to moderate activities with the most active one being azadironolide, IC50 2.4±0.03 μM and 1.1±0.01 μM against the D6 and W2 strains of Plasmodium falciparum, respectively; all other compounds possessed IC50 14.4–40.5 μM. None of the compounds showed significant cytotoxicity against vero cells, yet four of them were toxic against the 4T1 and HEp2 cancer cell lines with piscidinol A having IC50 8.0±0.03 and 8.4 ±0.01 μM against the 4T1 and HEp2 cells, respectively. Diacetylation of piscidinol A resulted in reduced cytotoxicity.ConclusionFrom the medicinal plants T. robusta and T. nilotica, twelve compounds were isolated and characterized; two of the isolated compounds, namely 11-epi-toonacilin and azadironolide showed good antiplasmodial activity with the highest selectivity indices.

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“…Phytochemically, a chemical characterization of Khaya senegalensis showed the presence of alkaloids, limonoids and terpenes and Melia azedarach polyphenol, flavonoids, tannins, alkaloids, sterols and polyterpenes and saponins. Several studies have described the antiplasmodial effect of its secondary metabolites 27,28,29,30,31,32,33 which could explain the observed results on the activity of extracts of Khaya senegalensis and Melia azedarach.…”

Antiplasmodial natural products: an update

“…Antiplasmodial assay of 14 Kenyan medicinal plants identified the methanol root bark extract of Turraea robusta (Meliaceae) as the most active against NF54 and K1 parasites (IC 50 = 2.4 and 3.5 µg/mL, respectively) [165]. Azadironolide ( 273 ) was subsequently isolated as the most active antiplasmodial compound from the plant stem bark with moderate cytotoxicity against Vero cells [166]. An ethnomedicinal survey of plant use in the Northern sector of Kibale National Park in western Uganda indicated that Neoboutonia macrocalyx (Euphorbiaceae) is used to treat malaria [167].…”

Molecular Farming in Artemisia annua, a Promising Approach to Improve Anti-malarial Drug Production

“…Interestingly, it is not only species in the Asiatic and Amazonian sub-areas, but Sub-Saharan Africa’s enormous plant biodiversity is also proving to be a source of new anti-malarial phyto-remedies. Useful chemical compounds, with anti-plasmodial activity, efficacy and safety have been found in endemic plants growing in this area, including Adansonia digitata , Azadirachta indica , Ficus sur , Cassia occidentalis , Cassia siamea , Nauclea latifolia , Plumbago Zeylanica , Tithonia diversifolia, Turraea robusta , Turraea nilotica , and Vernonia amygdalina ( Chinsembu, 2015 ; Irungu et al, 2015 ). However, excluding quinine, due to the insurgence of resistance to it, and all the potential therapeutic plants already described, nowadays the most widely used and efficient ACTs are those combining natural AN or chemically AN-synthesized derivates, such as artesunate and artemether ( Ajayi et al, 2008 ; WHO, 2014b ).…”