Bioactivity guided fractionation of Icacina trichantha Oliv. (Icacinaceae) tuber for antimalarial activity against Plasmodium berghei infected mice and GC-MS profile of bioactive fraction

Aqueous methanol extract of the tuber of Icacina trichantha was prepared using cold maceration and dried in vacuo at 40°C. The extract was purified using solvent-solvent partitioning with n-hexane, dichloromethane, ethyl acetate, n-butanol. n-Hexane fraction was purified using Vacuum Liquid Chromatography, eluting with a gradient of dichloromethane in methanol (9:1, 7:3, 5:5, 0:10, each 500 mL) to obtain four sub-fractions. Acute toxicity study was done using Lorke’s method while in vivo anti-malarial study was carried out using suppressive model. Phytochemical analysis was carried out using standard procedure and most active sub-fraction was subjected to gas chromatography-mass spectroscopy. The extract at doses of 100, 200 and 400 mg/kg caused a significant (p<0.001) increase in percentage suppression of Plasmodium: 91.54 %, 94.48 % and 94.58% respectively. Phytochemical analysis of the extract revealed the presence of alkaloids, tannins, flavonoids saponin, glycoside, terpenoids, phenols, steroids, carbohydrates, reducing sugars. The GC-MS analysis showed the presence of eighteen compounds, the most abundant compound includes 9- octadecenoic acid (Z)-, methyl ester (oleic acid, 15.30%), 9, 12-octadecadienoic acid (Z, Z), methyl ester (linoleic acid, 14.34%). These findings suggest scientific evidence in support to the use of I. trichantha tuber for the management of malaria

Steroid Alkaloids from Holarrhena africana with Strong Activity against Trypanosoma brucei rhodesiense

In our continued search for natural compounds with activity against Trypanosoma brucei, causative agent of human African trypanosomiasis (HAT, "sleeping sickness"), we have investigated extracts from the leaves and bark of the West African Holarrhenaafricana (syn. Holarrhena floribunda; Apocynaceae). The extracts and their alkaloid-enriched fractions displayed promising in vitro activity against bloodstream forms of T. brucei rhodesiense (Tbr; East African HAT). Bioactivity-guided chromatographic fractionation of the alkaloid-rich fractions resulted in the isolation of 17 steroid alkaloids, one nitrogen-free steroid and one alkaloid-like non-steroid. Impressive activities (IC50 in µM) against Tbr were recorded for 3β-holaphyllamine (0.40 ± 0.28), 3α-holaphyllamine (0.37 ± 0.16), 3β-dihydroholaphyllamine (0.67 ± 0.03), N-methylholaphyllamine (0.08 ± 0.01), conessimine (0.17 ± 0.08), conessine (0.42 ± 0.09), isoconessimine (0.17 ± 0.11) and holarrhesine (0.12 ± 0.08) with selectivity indices ranging from 13 to 302. Based on comparison of the structures of this congeneric series of steroid alkaloids and their activities, structure-activity relationships (SARs) could be established. It was found that a basic amino group at position C-3 of the pregnane or pregn-5-ene steroid nucleus is required for a significant anti-trypanosomal activity. The mono-methylated amino group at C-3 represents an optimum for activity. ∆(5,6) unsaturation slightly increased the activity while hydrolysis of C-12β ester derivatives led to a loss of activity. An additional amino group at C-20 engaged in a pyrrolidine ring closed towards C-18 significantly increased the selectivity index of the compounds. Our findings provide useful empirical data for further development of steroid alkaloids as a novel class of anti-trypanosomal compounds which represent a promising starting point towards new drugs to combat human African trypanosomiasis

A 3D-QSAR Study on the Antitrypanosomal and Cytotoxic Activities of Steroid Alkaloids by Comparative Molecular Field Analysis

As part of our research for new leads against human African trypanosomiasis (HAT), we report on a 3D-QSAR study for antitrypanosomal activity and cytotoxicity of aminosteroid-type alkaloids recently isolated from the African medicinal plant Holarrhena africana A. DC. (Apocynaceae), some of which are strong trypanocides against Trypanosoma brucei rhodesiense (Tbr), with low toxicity against mammalian cells. Fully optimized 3D molecular models of seventeen congeneric Holarrhena alkaloids were subjected to a comparative molecular field analysis (CoMFA). CoMFA models were obtained for both, the anti-Tbr and cytotoxic activity data. Model performance was assessed in terms of statistical characteristics (R2, Q2, and P2 for partial least squares (PLS) regression, internal cross-validation (leave-one-out), and external predictions (test set), respectively, as well as the corresponding standard deviation error in prediction (SDEP) and F-values). With R2 = 0.99, Q2 = 0.83 and P2 = 0.79 for anti-Tbr activity and R2 = 0.94, Q2 = 0.64, P2 = 0.59 for cytotoxicity against L6 rat skeletal myoblasts, both models were of good internal and external predictive power. The regression coefficients of the models representing the most prominent steric and electrostatic effects on anti-Tbr and for L6 cytotoxic activity were translated into contour maps and analyzed visually, allowing suggestions for possible modification of the aminosteroids to further increase the antitrypanosomal potency and selectivity. Very interestingly, the 3D-QSAR model established with the Holarrhena alkaloids also applied to the antitrypanosomal activity of two aminocycloartane-type compounds recently isolated by our group from Buxus sempervirens L. (Buxaceae), which indicates that these structurally similar natural products share a common structure–activity relationship (SAR) and, possibly, mechanism of action with the Holarrhena steroids. This 3D-QSAR study has thus resulted in plausible structural explanations of the antitrypanosomal activity and selectivity of aminosteroid- and aminocycloartane-type alkaloids as an interesting new class of trypanocides and may represent a starting point for lead optimization

Anti-Trypanosomal Activity of Nigerian Plants and Their Constituents

African trypanosomiasis is a vector-borne parasitic disease causing serious risks to the lives of about 60 million people and 48 million cattle globally. Nigerian medicinal plants are known to contain a large variety of chemical structures and some of the plant extracts have been screened for antitrypanosomal activity, in the search for potential new drugs against the illness. We surveyed the literatures on plants and plant-derived products with antitrypanosomal activity from Nigerian flora published from 1990 to 2014. About 90 plants were identified, with 54 compounds as potential active agents and presented by plant families in alphabetical order. This review indicates that the Nigerian flora may be suitable as a starting point in searching for new and more efficient trypanocidal molecules

Two trypanocidal dipeptides from the roots of Zapoteca portoricensis (Fabaceae)

Zapoteca portoricensis (Jacq) HM Hernández is used with remarkable efficacy in ethnomedicinal management of tonsillitis in the Eastern part of Nigeria. Previous pharmacological studies have validated the antiinflammatory and antimicrobial activities of the crude extract. In this study, two dipeptides, saropeptate (aurantiamide acetate) and anabellamide, were isolated from the methanol root extract of Zapoteca portoricensis and their chemical structures deduced by one dimensional and two dimensional NMR and mass spectrometry. These compounds were isolated for the first time from this plant, and no report has been found on their previous isolation from the genus Zapoteca. Evaluation of their trypanocidal activity showed that compound 1 exhibited potent activity against Trypanosoma brucei rhodesiense with an IC50 value of 3.63 μM and selectivity index of 25.3

Molecular Modeling of Potential Anticancer Agents from African Medicinal Plants

Naturally occurring anticancer compounds represent about half of the chemotherapeutic drugs which have been put in the market against cancer until date. Computer-based or in silico virtual screening methods are often used in lead/hit discovery protocols. In this study, the "drug-likeness" of similar to 400 compounds from African medicinal plants that have shown in vitro and/or in vivo anticancer, cytotoxic, and antiproliferative activities has been explored. To verify potential binding to anticancer drug targets, the interactions between the compounds and 14 selected targets have been analyzed by in silk modeling. Docking and binding affinity calculations were carried out, in comparison with known anticancer agents comprising similar to 1 500 published naturally occurring plant-based compounds from around the world. The results reveal that African medicinal plants could represent a good starting point for the discovery of anticancer drugs. The small data set generated (named AfroCancer) has been made available for research groups working on virtual screening

New neolignan glycoside and an unusual benzoyl malic acid derivative from <i>Maytenus senegalensis</i> leaves

<div><p>Further investigation of the methanol leaf extract of <i>Maytenus senegalensis</i> led to the isolation of six compounds, including mayselignoside (<b>1</b>) and an unusual benzoyl malic acid derivative, benzoyl <i>R</i>-(+)-malic acid (<b>2</b>). Two known lignan derivatives (+)-lyoniresinol (<b>3</b>) and ( − )-isolariciresinol (<b>4</b>), a known neolignan derivative dihydrodehydrodiconiferyl alcohol (<b>5</b>) and the triterpenoid, β-amyrin (<b>6</b>) were also isolated. The structures of these compounds were elucidated by a combination of 1D and 2D NMR and mass spectroscopy. All compounds were tested for cytotoxicity against mouse lymphoma cell line (L5178Y) and for antimicrobial activity against strains of bacteria and fungi. None of the compounds showed promising cytotoxic and/or antimicrobial activities.</p></div

Molecular Modeling of Potential Anticancer Agents from African Medicinal Plants

Naturally occurring anticancer compounds represent about half of the chemotherapeutic drugs which have been put in the market against cancer until date. Computer-based or <i>in silico</i> virtual screening methods are often used in lead/hit discovery protocols. In this study, the “drug-likeness” of ∼400 compounds from African medicinal plants that have shown <i>in vitro</i> and/or <i>in vivo</i> anticancer, cytotoxic, and antiproliferative activities has been explored. To verify potential binding to anticancer drug targets, the interactions between the compounds and 14 selected targets have been analyzed by <i>in silico</i> modeling. Docking and binding affinity calculations were carried out, in comparison with known anticancer agents comprising ∼1 500 published naturally occurring plant-based compounds from around the world. The results reveal that African medicinal plants could represent a good starting point for the discovery of anticancer drugs. The small data set generated (named AfroCancer) has been made available for research groups working on virtual screening