α-Amylase and α-glucosidase inhibitors from Zanthoxylum chalybeum Engl. root bark.

A systematic analysis of the root bark of Zanthoxylum chalybeum was conducted to establish the antidiabetic potential of isolated compounds based on its ethnomedicinal use to manage diabetes. Chromatographic separation of alkaloid extracts led to isolation of three undescribed amides, chaylbemide A (1), chalybemide B (2) and chalybemide C (3) alongside the known fagaramide (4); four known benzophenanthridine alkaloids skimmianine (5), norchelerythrine (6), 6-acetonyldihydrochelerythrine (7) and 6-hydroxy-N-methyl decarine (8). The alkaloid free extracts yielded three known lignans, ailanthoidol (9), 2,3-epoxy-6,7-methylenedioxy coniferyl alcohol (10), sesamine (11), together with five known triterpenoids, lupeol (12), lupanone (13), 3α,20-dihydroxy-28-lupanoic acid (14), 20-hydroxy-3-oxo-28-lupanoic acid (15) and 3α,20,28-trihydroxylupane (16). The structures of the compounds were established based on 1D and 2D NMR spectroscopic and mass spectrometric experiments. Compounds 1-8 displayed inhibitory activities against both α-amylase and α-glycosidase in the range of IC50 = 43.22-49.36 µM which showed no significant (P > 0.05) difference to the positive control acarbose (IC50 = 42.67; 44.88 µM). The results confirmed anti-hyperglycemic potential of alkaloids from Z. chalybeum which lends credence to its use towards management of diabetes susceptibilities.

Prospects for malaria control through manipulation of mosquito larval habitats and olfactory-mediated behavioural responses using plant-derived compounds.

Malaria presents an overwhelming public health challenge, particularly in sub-Saharan Africa where vector favourable conditions and poverty prevail, potentiating the disease burden. Behavioural variability of malaria vectors poses a great challenge to existing vector control programmes with insecticide resistance already acquired to nearly all available chemical compounds. Thus, approaches incorporating plant-derived compounds to manipulate semiochemical-mediated behaviours through disruption of mosquito olfactory sensory system have considerably gained interests to interrupt malaria transmission cycle. The combination of push-pull methods and larval control have the potential to reduce malaria vector populations, thus minimising the risk of contracting malaria especially in resource-constrained communities where access to synthetic insecticides is a challenge. In this review, we have compiled information regarding the current status of knowledge on manipulation of larval ecology and chemical-mediated behaviour of adult mosquitoes with plant-derived compounds for controlling mosquito populations. Further, an update on the current advancements in technologies to improve longevity and efficiency of these compounds for field applications has been provided.

Noncanonical amino acids to improve the pH response of pHLIP insertion at tumor acidity.

The pH low insertion peptide (pHLIP) offers the potential to deliver drugs selectively to the cytoplasm of cancer cells based on tumor acidosis. The WT pHLIP inserts into membranes with a pH50 of 6.1, while most solid tumors have extracellular pH (pH(e)) of 6.5-7.0. To close this gap, a SAR study was carried out to search for pHLIP variants with improved pH response. Replacing Asp25 with α-aminoadipic acid (Aad) adjusts the pH50 to 6.74, matching average tumor acidity, and replacing Asp14 with γ-carboxyglutamic acid (Gla) increases the sharpness of pH response (transition over 0.5 instead of 1 pH unit). These effects are additive: the Asp14Gla/Asp25Aad double variant shows a pH50 of 6.79, with sharper transition than Asp25Aad. Furthermore, the advantage of the double variant over WT pHLIP in terms of cargo delivery was demonstrated in turn-on fluorescence assays and anti-proliferation studies (using paclitaxel as cargo) in A549 lung cancer cells at pH 6.6.