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

• Ethnopharmacological relevance: Turraea 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 methods: From 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). Results: The 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. Conclusion: From 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. © 2015 The Authors. Published by Elsevier Ireland Ltd.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)

NATURVETENSKAP  -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)

NATURVETENSKAP  -- Kemi -- Organisk kemi (hsv//swe)

NATURAL SCIENCES  -- Chemical Sciences -- Organic Chemistry (hsv//eng)

Nyckelord

Antiplasmodial activity

Azadironolide

Cytotoxicity

Limonoid

Toonacilin

Toonapubesins F

Turraea nilotica

Turraea robusta

11 epi toonacillin

12alpha acetoxy 7 deacetylazadirone

1alpha

3alpha diacety 7alpha tigloyvillasinin

antimalarial agent

azadirone

chloroquine

glucoside

hispidol B

hypoxanthine

mzikonone

niloticin

phytosterol

piscidinol A

plant extract

plant medicinal product

protolimonoid

sitosterol 3 o beta dextro glucopyranoside

stigmasterol

stigmasterol 3 o beta dextro glucopyranoside acetate

toonapubesin F

Turraea nilotica extract

Turraea robusta extract

turranolide

unclassified drug

acetylation

animal cell

antimalarial activity

Article

bark

breast cancer

controlled study

HEp 2 cell line

human

human cell

larynx carcinoma

medicinal plant

mouse

nonhuman

Plasmodium falciparum

Vero cell line

X ray crystallography

X ray diffraction

Antiplasmodial activity

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