Development of therapeutics for treatment of Ebola virus infection

Ebola virus infection can cause Ebola virus disease (EVD). Patients usually show severe symptoms, and the fatality rate can reach up to 90%. No licensed medicine is available. In this review, development of therapeutics for treatment of Ebola virus infection and EVD will be discussed.     

α-Glucosidase inhibition activity and in silico study of 2-(benzo[d][1,3]dioxol-5-yl)-4H-chromen-4-one,a synthetic derivative of flavone

A synthetic flavone derivative 2-(benzo[d][1,3]dioxol-5-yl)-4H-chromen-4-one (BDC) was synthesized by the one pot reaction method and assessed for α-glucosidase inhibitory activity. The BDC demonstrated dose dependent inhibition of α-glucosidase activity. A maximum inhibition (99.3 ± 0.26%) of α-glucosidase was observed at 27.6 µM. The maximum α-glucosidase inhibitory activity depicted by BDC 27.6 µM concentration was 22.4 fold over the maximum inhibition observed with acarbose (97.72 ± 0.59% at 669.57 µM), a standard commercial anti-diabetic drug. In contrast to acarbose that depicted competitive type inhibition, kinetic studies of α-glucosidase inhibition by BDC demonstrated non-competitive inhibition with Km of 0.71 mM⁻¹ and a Vmax of 0.028 mmol/min. In silico studies suggest allosteric interaction of BDC with α-glucosidase at a minimum binding energy (ΔG) of −8.64 kcal/mol and Ki of 465.3 nM, whereas, acarbose interacted at the active site of α-glucosidase with ΔG of −9.23 kcal/mol and Ki of 172 nM. Thus BDC significantly inhibited α-glucosidase in comparison to acarbose. Moreover, BDC has been endorsed for drug likeness by evaluating it as per Lipinski rule of five. Thus, BDC can be a lead compound for the management of type-2 diabetes mellitus.     

Synthesis,antiproliferative and antibacterial activity of new amides of salinomycin

A series of 11 novel amides of salinomycin were synthesized for the first time. All the obtained compounds were found to show potent antiproliferative activity against human cancer cell lines including the drug-resistant cancer cells. Four new salinomycin derivatives revealed good antibacterial activity against clinical isolates of methicillin-resistant Staphylococcus epidermidis (MRSE).     

Computational Oral Absorption Simulation for Low‐Solubility Compounds

Bile micelles play an important role in oral absorption of low‐solubility compounds. Bile micelles can affect solubility, dissolution rate, and permeability. For the pH–solubility profile in bile micelles, the Henderson–Hasselbalch equation should be modified to take bile‐micelle partition into account. For the dissolution rate, in the Nernst–Brunner equation, the effective diffusion coefficient in bile‐micelle media should be used instead of the monomer diffusion coefficient. The diffusion coefficient of bile micelles is 8‐ to 18‐fold smaller than that of monomer molecules. For permeability, the effective diffusion coefficient in the unstirred water layer adjacent to the epithelial membrane, and the free fraction at the epithelial membrane surface should be taken into account. The importance of these aspects is demonstrated here using several in vivo and clinical oral‐absorption data of low‐solubility model compounds. Using the theoretical equations, the food effect on oral absorption is further discussed.     

Ferulic acid–carbazole hybrid compounds: Combination of cholinesterase inhibition,antioxidant and neuroprotection as multifunctional anti-Alzheimer agents

In order to search for novel multifunctional anti-Alzheimer agents, a series of ferulic acid–carbazole hybrid compounds were designed and synthesized. Ellman’s assay revealed that the hybrid compounds showed moderate to potent inhibitory activity against the cholinesterases. Particularly, the AChE inhibition potency of compound 5k (IC₅₀ 1.9 μM) was even 5-fold higher than that of galantamine. In addition, the target compounds showed pronounced antioxidant ability and neuroprotective property, especially against the ROS-induced toxicity. Notably, the neuroprotective effect of 5k was obviously superior to that of the mixture of ferulic acid and carbazole, indicating the therapeutic effect of the hybrid compound is better than the combination administration of the corresponding mixture.     

Two new compounds with antimicrobial activities from the seeds of Voacanga africana

Two new compounds, (R)-4-(2-methylpentyl)-4H-dithieno[2,3-b:3′,2′-e]pyran (1) and 4-(2-ethylbutyl)-4H-dithieno[2,3-b:3′,2′-e]pyran (2) were extracted from the seeds of Voacanga africana. The molecular structures of these compounds were measured with the help of broad spectroscopic (1D and 2D-NMR, IR, ESI-TOF-MS, HR-MS) analyses. The primary pharmacological operations of these compounds were brought to evaluation by applying the antibacterial extrasomatic test. The results revealed that compound 1 and 2 were in an effective position to stop the growth of Escherichia coli, Streptococcus and Salmonella typhi. On the other hand, the inhibitory impacts on Staphylococcus aureus as well as Pseudomonas aeruginosa were not apparent.     

Comparisons of deterrency and toxicity of selected secondary plant compounds to an oligophagous and a polyphagous acridid

A comparison was made of the relationship between deterrence and toxicity of eight secondary compounds to two acridids. The grass specialist Locusta migratoria was compared with the polyphagous Schistocerca gregaria. L. migratoria was deterred by all compounds presented at natural concentrations to which S. gregaria showed a variety of behavioral responses. Overall, L. migratoria was significantly more susceptible to toxic effects of the chemicals when injected into the hemolymph than was S. gregaria and was more sensitive behaviourally to them. There was a significant correlation in both species between deterrency and toxicity of injected compounds, but little evidence of a relationship between deterrency and oral toxicity.

---

Résumé La comparaison a porté sur les relations entre répulsion et toxicité de huit substances secondaires chez deux acridiens: Locusta migratoria, spécialiste de graminées, et Schistocerca gregaria, polyphage. L. migratoria est repoussé par toutes les substances proposées, aux concentrations naturelles, pour lesquelles S. gregaria a présenté des comportements trés divers. Mais surtout, L. migratoria a été significativement plus sensible que S. gregaria aux effets toxiques de ces substances quand elles sont injectées dans son haemolymphe; S. gregaria a réagi à ces substances plus par des modifications de son comportement. Il y a une corrélation significative pour les deux espèces, entre la répulsion et la toxicité des substances injectées.

     

Advances in improvement of quality and resistance in a multipurpose crop: sea buckthorn

Sea buckthorn is a berry crop with multiple uses. The berries are highly appreciated for their unique taste but are also very rich in bioactive compounds with powerful nutritional and medicinal values. In addition, the plants grow well under adverse conditions, and are often used to fight soil erosion. Utilization of sea buckthorn has therefore increased around the world but serious problems have, nevertheless, been encountered due to drought, salinity, diseases and insect pests. This review covers important aspects of sea buckthorn research, such as heritable and environmentally induced variation in biochemical compounds, causes and effects of the devastating dried-shrink disease, susceptibility to insect pests, methods for conventional breeding, and the utilization of DNA markers for taxonomical and population genetic analyses, and for investigating the inheritance of quality and resistance traits. We also present possibilities to implement innovative biotechnological breeding methods, especially metabolite profiling and MAS/GRC-based markers, for fast and efficient development of elite genotypes with specific nutritional- and health-related bioactive compounds and strong resistance to biotic and abiotic stress.     

Optional tool use: The case of wild bearded capuchins (Sapajus libidinosus) cracking cashew nuts by biting or by using percussors

Tool use in humans can be optional, that is, the same person can use different tools or no tool to achieve a given goal. Strategies to reach the same goal may differ across individuals and cultures and at the intra‐individual level. This is the first experimental study at the intra‐individual level on the optional use of a tool in wild nonhuman primates. We investigated optional tool use by wild bearded capuchins (Sapajus libidinosus) of Fazenda Boa Vista (FBV; Piauí, Brazil). These monkeys habitually succeed in cracking open the mesocarp of dry cashew nuts (Anacardium spp.) by pounding them with stones and/or by biting. We assessed whether availability of a stone and resistance of the nut affected capuchins' choice to pound or to bite the nuts and their rates of success. Sixteen capuchins (1–16 years) received small and large dry cashew nuts by an anvil together with a stone (Stone condition) or without a stone (No‐Stone condition). In the Stone conditions, subjects used it to crack the nut in 89.1% (large nuts) and 90.1% (small nut) of the trials. Nut size significantly affected the number of strikes used to open it. Availability of the stone significantly increased the average percent of success. In the No‐Stone conditions, monkeys searched for and used other percussors to crack the nuts in 54% of trials. In all conditions, age affects percentage of success and number of strikes to reach success. We argue that exclusive use of stones in other sites may be due to the higher abundance of stones at these sites compared with FBV. Since capuchins opened cashews with a tool 1–2 years earlier than they succeed at cracking more resistant palm nuts, we suggest that success at opening cashew nuts with percussors may support the monkeys' persistent efforts to crack palm nuts.     

Phenolic constituents of the cell walls of monocotyledons

Monocotyledons of 104 species in 52 families were divided into two groups depending on the UV fluorescence behaviour of their cell walls. The unlignified cell walls of the first group, fluoresced blue, which changed to green with increased intensity after treatment with NH₃ due to the presence of bound ferulic acid. The isolated cell walls of members of the first group were shown to contain bound ferulic, p-coumaric and diferulic acids. These acids were absent from cell walls of the second group. The first group contained families of the Commelinidae of Cronquist, the Palmae (part of the Arecidae), and the Philydraceae, Pontederiaceae, and Haemodoraceae (all part of Liliidae). The other families of the latter two subclasses and those of the Alismatidae belonged to the second group.