In vitro anti-plasmodial activity of Dicoma anomala subsp. gerrardii (Asteraceae): identification of its main active constituent, structure-activity relationship studies and gene expression profiling

<p>Abstract</p> <p>Background</p> <p>Anti-malarial drug resistance threatens to undermine efforts to eliminate this deadly disease. The resulting omnipresent requirement for drugs with novel modes of action prompted a national consortium initiative to discover new anti-plasmodial agents from South African medicinal plants. One of the plants selected for investigation was <it>Dicoma anomala </it>subsp. <it>gerrardii</it>, based on its ethnomedicinal profile.</p> <p>Methods</p> <p>Standard phytochemical analysis techniques, including solvent-solvent extraction, thin-layer- and column chromatography, were used to isolate the main active constituent of <it>Dicoma anomala </it>subsp. <it>gerrardii</it>. The crystallized pure compound was identified using nuclear magnetic resonance spectroscopy, mass spectrometry and X-ray crystallography. The compound was tested <it>in vitro </it>on <it>Plasmodium falciparum </it>cultures using the parasite lactate dehydrogenase (pLDH) assay and was found to have anti-malarial activity. To determine the functional groups responsible for the activity, a small collection of synthetic analogues was generated - the aim being to vary features proposed as likely to be related to the anti-malarial activity and to quantify the effect of the modifications <it>in vitro </it>using the pLDH assay. The effects of the pure compound on the <it>P. falciparum </it>transcriptome were subsequently investigated by treating ring-stage parasites (alongside untreated controls), followed by oligonucleotide microarray- and data analysis.</p> <p>Results</p> <p>The main active constituent was identified as dehydrobrachylaenolide, a eudesmanolide-type sesquiterpene lactone. The compound demonstrated an <it>in vitro </it>IC₅₀of 1.865 μM against a chloroquine-sensitive strain (D10) of <it>P. falciparum</it>. Synthetic analogues of the compound confirmed an absolute requirement that the α-methylene lactone be present in the eudesmanolide before significant anti-malarial activity was observed. This feature is absent in the artemisinins and suggests a different mode of action. Microarray data analysis identified 572 unique genes that were differentially expressed as a result of the treatment and gene ontology analysis identified various biological processes and molecular functions that were significantly affected. Comparison of the dehydrobrachylaenolide treatment transcriptional dataset with a published artesunate (also a sesquiterpene lactone) dataset revealed little overlap. These results strengthen the notion that the isolated compound and the artemisinins have differentiated modes of action.</p> <p>Conclusions</p> <p>The novel mode of action of dehydrobrachylaenolide, detected during these studies, will play an ongoing role in advancing anti-plasmodial drug discovery efforts.</p

β-Hydroxy sulfides and their syntheses

Sulfur-containing natural products are ubiquitous in nature, their most abundant source being marine organisms since sulfur, in the form of the sulfate ion, is the second most abundant anion in sea water after chloride. As part of natural products, sulfur can appear in a multitude of combinations and oxidation states: thiol, sulfide (acyclic or heterocyclic), disulfide, sulfoxide, sulfonate, thioaminal, hemithioacetal, various thioesters, thiocarbamate and isothiocyanate. This review article focuses on β-hydroxy sulfides and analogs; their presence in natural products, general protocols for their synthesis, and examples of their application in target oriented synthesis

An insight into a novel calixarene-sensitized Calix@Nb2CTx/g-C3N4 MXene-based photocatalytic heterostructure: Fabrication, physicochemical, optoelectronic, and photoelectrochemical properties

The development of highly efficient and cost-effective multifunctional photocatalysts is of current global interest because these photocatalysts have the potential to address the energy and water crisis. Herein, an efficient calixarene-based Calix@Nb2CTx/g-C3N4 (Cx–Nb–CN) photocatalyst was prepared through the formation of covalent bonds between the calixarene (Cx–COCl), g-C3N4 (CN), and Nb2CTx MXene. Enhanced optoelectronic and photoelectrochemical (PEC) properties were observed upon introducing Cx–COCl calixarene and Nb2CTx complexes to the g-C3N4 (CN) photocatalyst. The XPS valence band measurements demonstrated the narrowing of the energy band gap for the composites due to the downshifting and upshifting of the CB and VB, correspondingly. Due to the sensitization effect, the Cx–CN presented superior photocatalytic properties relative to the pristine CN. Moreover, reduced charge transfer resistance (Rct = 110.7 Ω cm2) and the highest photocurrent density (Jp = 7.95 mA/cm2) were observed for the Cx–Nb–CN–5 heterostructure. The Schottky-heterostructures Cx–Nb–CN–1, Cx–Nb–CN–3, and Cx–Nb–CN–5 presented high linear sweep current densities (JLSV) of 8.61, 12.39, 14.04 mA/cm2 signifying excellent light utilization and efficient separation of charge carriers, respectively. The fabricated photocatalyst exhibits excellent physicochemical and photocatalytic properties with the potential to facilitate host-guest complexation towards environmental detoxification and energy conversions

Traditional uses, phytochemistry, pharmacology and other potential applications of Vitellaria paradoxa Gaertn. (Sapotaceae): A review

Vitellaria paradoxa Gaertn. is a multipurpose medicinal plant of the family Sapotaceae, and it has been widely used usually in the clinical traditional medicine as remedy for a wide range of diseases for several decades. In addition, the plant has also found applications in confectionery, cosmetics and soaps, and pharmaceuticals both locally and internationally. V. paradoxa, which has been identified with >150 phytoconstituents, is rich in oleanane-type triterpene acids and glycosides, such as paradoxosides A-E, tieghemelin A, parkiosides A-C, bassic acid, as well as flavonoids such as quercetin and catechin-type compounds. The extracts and the active constituents of V. paradoxa have been investigated for various pharmacological activities, including but not limited to anticancer, melanogenesis-inhibitory, antibacterial, anti-diabetic, antioxidant, anti-inflammatory, anti-diarrhoeal, and antifungal activities. Additionally, V. paradoxa has also been utilized in nanoparticles (NPs) synthesis. These NPs among other things have shown significant antinociceptive and antiedematogenic activities as well as environmental friendly adsorptive properties for the removal of pollutants from pharmaceutical effluents. Overall, this review comprehensively examines the traditional uses, phytochemistry, pharmacology, toxicology, clinical studies, and nanoparticles synthesized from V. paradoxa and their applications

Pentacyclic Triterpenoids, Phytosteroids and Fatty Acid Isolated from the Stem-bark of Cola lateritia K. Schum. (Sterculiaceae) of Cameroon origin; Evaluation of Their Antibacterial Activity

The phytochemical investigation on the chemical constituents of dichloromethane-methanol (1:1) stem-bark extract ofCola lateritiaK. Schum. (Sterculiaceae) led to the isolationand characterization of five pentacyclic triterpenoids, one fatty acid and two phytosteroids. Thecompounds were identified as heptadecanoic acid (1), maslinic acid (2), betulinic acid (3), lupenone(4), lupeol (5), friedelin (6),b-stigmasterol (7) andß-sitosterol-3-O-ß-D-glucoside (8). Their struc-tures were determined by NMR analysis (1H,13C, DEPT-135, COSY, HMBC and HSQC), high-resolution mass spectrometry (HR-ESI-MS) and comparisons with published data in the literature.This work, to the best of our knowledge, is the first isolation and identification of these compoundsin pure forms fromCola lateritia. Also, compounds1–3are reported for the first time fromColagenus.In vitroantibacterial activity of the isolated compounds (1–8) and the crude extract wereevaluated againstBacillus subtilis,Staphylococcus epidermidis,Enterococcus faecalis,Mycobacterium smegmatis,Staphylococcus aureus,Enterobacter cloacae,Klebsiella oxytoca,Proteusvulgaris,Klebsiella pneumonia,Escherichia coli, Proteus mirabilisandKlebsiella aerogeneswithstreptomycin, nalidixic acid and ampicillin as standard antibacterial drugs. Compound2was activeagainstE. faecalis(MIC = 18.5mg/mL), and it was 6.9 and 28 times lower and active than that ofstreptomycin (MIC 128mg/mL) and nalidixic acid (MIC>512mg/mL) respectively. All the isolatedcompounds and crude extract showed significant activities against the tested bacterial strains.National Research Foundatio