Selective activity of extracts of Margaritaria discoidea and Homalium africanum on Onchocerca ochengi

<p>Abstract</p> <p>Background</p> <p>The current treatment of onchocerciasis relies on the use of ivermectin which is only microfilaricidal and for which resistant parasite strains of veterinary importance are increasingly being detected. In the search for novel filaricides and alternative medicines, we investigated the selective activity of crude extracts of <it>Margaritaria discoidea </it>and <it>Homalium africanum </it>on <it>Onchocerca ochengi</it>, a model parasite for <it>O. volvulus</it>. These plants are used to treat the disease in North West Cameroon.</p> <p>Methods</p> <p>Sixteen crude extracts were prepared from various parts of <it>M. discoidea </it>and <it>H. africanum </it>using different organic solvents. The filaricidal activities were determined <it>in vitro</it>. Cytotoxicity of the active extracts was assessed on monkey kidney epithelial cells <it>in vitro </it>and the selectivity indices (SI) of the extracts determined. Acute toxicity of the promising extracts was investigated in mice.</p> <p>Results</p> <p>Four out of the 16 extracts showed microfilaricidal activity based on motility reduction, whereas, none showed macrofilaricidal activity based on the MTT/formazan assay. The methylene chloride extract of <it>H. africanum </it>leaves (HLC) recorded the lowest IC₅₀of 31.25 μg/mL and an IC₁₀₀of 62.5 μg/mL. The SI for the active extracts ranged from 0.5 - 2.63. No form of acute toxicity was observed in mice. Phytochemical analysis revealed the presence of anthraquinones, sterols and terpenoids in the promising extracts.</p> <p>Conclusions</p> <p>The non-polar extracts of <it>M. discoidea </it>and <it>H. africanum </it>are potential sources of new microfilaricidal lead compounds, and the results support their use in traditional medicine.</p

Antiparasitic Sesquiterpenes from the Cameroonian Spice Scleria striatinux and Preliminary In Vitro and In Silico DMPK Assessment

Abstract The antiparasitic activity and preliminary in vitro and in silico drug metabolism and pharmacokinetic (DMPK) assessment of six isomeric sesquiterpenes (1–6), isolated from the Cameroonian spice Scleria striatinux De Wild (Cyperaceae) is reported. The study was prompted by the observation that two of the compounds (1 and 2) exhibited varying levels of antiparasitic activity on Plasmodium falciparum, Trypanosoma brucei rhodesiense, Trypanosoma cruzi and Leishmania donovani. The in silico method employed a total of 46 descriptors, calculated using Schrödinger QikProp software. 18 of these molecular descriptors that are often used to predict DMPK profiles of drug-like molecules have been selected for discussion. In vitro experimental assessment of metabolic stability made use of human liver microsomes, which was used to correlate theoretical predictions with experimental findings. Overall, the test compounds have been found to have acceptable physicochemical properties and fall within the ranges associated with “drug-like” molecules. Moreover, the compounds exhibited minimal degradation in incubations with human liver microsomes. Although some of these compounds have been reported previously (1, 2, 4 and 5), this is the first report on their antiparasitic activities, as well as assessment of their DMPK profiles. These results have therefore provided a window for further development of this novel class of sesquiterpene molecules as potential antiparasitic drugs. Graphical Abstrac

Evaluation of anti-onchocercal activity of pseudopalmatine, a quaternary protoberberine alkaloid of Enantia chlorantha (Syn. Annickia chlorantha)

As part of our efforts towards identifying and subsequently developing lead compounds from medicinal plants of Cameroon to combat neglected tropical diseases, we embarked to phytochemically investigate Enantia chlorantha (Syn. Annickia chlorantha). The rationale for choosing this plant is its numerous uses in folk medicine in Cameroon and other parts of Africa. In Cameroon the quaternary protoberberine alkaloids, columbamine (2), palmatine (3) and jatrorrizine (4) have been isolated from the stem back and combined to produce a phytomedicine (HEPAZOR®) used in the treatment of viral hepatitis. An alkaloidal extraction of the methanolic extract of the stem bark of the plant was carried-out and this afforded yellow amorphous solids whose structure was obtained using routine nuclear magnetic resonance spectroscopy (NMR), high pressure liquid  chromatography coupled to an electrospray mass spectrometer (HPLC-ESI-MS) and comparison with literature. The compound was identified as   pseudopalmatine (1), a quaternary protoberberine alkaloid. Preliminary screening of the compound on both adult and juvenile worms of Onchocerca ochengi, a close relative of Onchocerca volvulus, the parasite responsible for human onchocerciasis (river blindness), showed that compound (1) was inactive at a concentration of 500 μg/mL on the adult worms, but inhibited microfilariae motility completely at this same concentration and by 50 % at 250 μg/mL and was thus considered active. While this work to the best of our knowledge constitutes the first report on the anti-onchocercal activity of quaternary protoberberine alkaloids in general and pseudopalmatine (1) in particular isolated from E. Chlorantha, it has however opened a window for further investigation of the anti-onchoceral activity of this class of  compounds.Key words: anti-onchocercal, pseudopalmatine, alkaloid, Enantia chloranth

Cytotoxicity of a new tirucallane derivative isolated from Stereospermum acuminatissimum K. Schum stem bark.

Leutcha BP, Sema DK, Dzoyem JP, et al. Cytotoxicity of a new tirucallane derivative isolated from Stereospermum acuminatissimum K. Schum stem bark. Natural product research. 2020:1-6.One new tirucallan derivative, leutcharic acid (1) was isolated from Stereospermum acuminatissimum stem bark together with the known compounds 3-oxo-22-hydroxyhopane (2), 3,4-secotirucalla-4(28),7,24-trien-3,21-dioic acid (3), 3-oxotirucalla-7,24-dien-21-oic acid (7), lupeol (4), beta-sitosterol (5) and stigmasterol (6). The structures of the isolated compounds were elucidated using 1D and 2D NMR spectroscopy in combination with literature data. To the best of our knowledge, this is the first report on the cytotoxic properties' constituents of S. acuminatissimum. Cytotoxicity of compounds 1 and 2 was assessed invitro with the WST-1 assay on human lung adenocarcinoma A549 and THP-1 human monocytic leukaemia cell lines. Both compounds showed antiproliferative activity on the cancer cells. Compound 2 was more active against THP-1 with an IC50 value of 26.83M. The sensitivity of THP-1 cells to compounds 1 and 2 indicated that these compounds might be potential leads for anticancer agent development against leukaemia