An one-pot synthesis of syn-2,3-epoxyalcohols from α,β-unsaturated ketones

Facile one-pot synthesis of syn-2,3-epoxyalcohols from α,β-unsaturated ketones was achieved by consecutive addition of diisobutylaluminium hydride and t-butyl hydroperoxide

Systematic review of climate change impact research in Nigeria: implication for sustainable development

There is evidence that Nigeria is already experiencing environmental challenges attributed to climate change (CC) and its impacts. This has clearly highlighted the need for knowledge-based strategies to help plan adequate mitigation and adaptation measures for the country. One of the basic requirements to ensure such strategies is the development of a database of national CC research. This will aid in the assessment of past and present scientific publications from which directions for future study can be mapped. The present study used standard, systematic, and bibliographic literature reviews to analyse the trend, focus, spatial variability, and effectiveness of published research on CC impacts in Nigeria. Four thematic areas of CC impact research were defined: Agriculture, Environment, Human and Multi-disciplinary study. A total of 701 articles were found to be relevant and the review shows that CC impacts and adaptations in the literature vary across research categories and locations. The period between 2011 (68 studies) and 2015 (80 studies) showed a tremendous rise in CC impact research with a peak in 2014 (84 studies). Studies in the agriculture category had the highest publications in 23 States of Nigeria. The review revealed three research gaps: (1) lack of research that investigated the magnitude of present and potential future impacts in the aquatic environment (2) little attention on CC impacts and adaptation in the Northern regions of Nigeria (3) absence of study investigating the effects of multiple variables of CC at the same time. The findings suggest that it would be useful to advance CC research in Nigeria beyond perceptive approaches to more quantitative ones. This is particularly important for highly vulnerable animals, crops, locations, and for better planning of adaptation strategies

Deoxycholic Acid-Derived Tetraoxane Antimalarials and Antiproliferatives

The synthesis of deoxycholic acid (DCA)- and cholic acid (CA)-derived mixed tetraoxanes revealed that N-(2-dimethylamino)ethyl derivatives are potent antimalarials in vitro and in vivo. The tetraoxanes presented in this paper are dual inhibitors: besides curing mice in vivo without observed toxic effects, they kill cancer cell lines at very low concentrations. For example, DCA and CA derivatives 16 and 25 cured 3/5 (160 mg/kg/day) and 2/5 (40 mg/kg/day, MTD gt 960 mg/kg), respectively, and they were extremely active against melanoma LOX IMVI cancer, LC50 = 22 nM and 69 nM, respectively

Second generation of diazachrysenes: Protection of Ebola virus infected mice and mechanism of action

Ebola virus (EBOV) causes a deadly hemorrhagic fever in humans and non-human primates. There is currently no FDA-approved vaccine or medication to counter this disease. Here, we report on the design, synthesis and anti-viral activities of two classes of compounds which show high potency against EBOV in both in vitro cell culture assays and in vivo mouse models Ebola viral disease. These compounds incorporate the structural features of cationic amphiphilic drugs (CAD), i.e they possess both a hydrophobic domain and a hydrophilic domain consisting of an ionizable amine functional group. These structural features enable easily diffusion into cells but once inside an acidic compartment their amine groups became protonated, ionized and remain trapped inside the acidic compartments such as late endosomes and lysosomes. These compounds, by virtue of their lysomotrophic functions, blocked EBOV entry. However, unlike other drugs containing a CAD moiety including chloroquine and amodiaquine, compounds reported in this study display faster kinetics of accumulation in the lysosomes, robust expansion of late endosome/lysosomes, relatively more potent suppression of lysosome fusion with other vesicular compartments and inhibition of cathepsins activities, all of which play a vital role in anti-EBOV activity. Furthermore, the diazachrysene 2 (ZSML08) that showed most potent activity against EBOV in in vitro cell culture assays also showed significant survival benefit with 100% protection in mouse models of Ebola virus disease, at a low dose of 10 mg/kg/day. Lastly, toxicity studies in vivo using zebrafish models suggest no developmental defects or toxicity associated with these compounds. Overall, these studies describe two new pharmacophores that by virtue of being potent lysosomotrophs, display potent anti-EBOV activities both in vitro and in vivo animal models of EBOV disease