Concise Synthesis of Photocleavable Molecular Tag for Laser Desorption Ionization Mass Spectrometry via Fries Reaction

A new synthetic route for the photocleavable molecular tag for laser desorption ionization mass spectrometry (LDI-MS) was achieved using Fries reaction of 2,6-dimethylphenyl ester as its key reaction. Zirconium chloride was found as uniquely efficient adjuvant to promote the reaction. The molecular tag was obtained in 5 steps without chromatographic purification

Antimalarial potential and phytochemical composition of fractions of Lippia kituiensis Vatke (Verbenaceae) growing in Northern Tanzania

This research article published by Journal of Medicinal Plants Research, 2020Despite past decades of steady advances in the fight against Malaria, statistics show that the disease is still a threat to human health. Previous successes in the development of antimalarial drugs from medicinal plants have fuelled research in this area. However, antimalarial studies on fractionated extracts from such plants have progressed slowly. This study reports the antimalarial potential of fractions from Lippia kituiensis Vatke, for the first time. Column chromatography was used during fractionation. Antiplasmodial assay against chloroquine-sensitive (D6) and resistant (W2) plasmodium strains were done using hypoxanthine incorporation assay. MTT assay was used to assess the cytotoxicity of fractions against the Vero cell line. Fractions obtained exhibited varied inhibitory concentrations (IC50); with the most efficacious being, Lk-5 (19.45 ± 6.20 μg/ml), Lk-3 (30.43 ± 0.68 μg/ml), Lk-4 (30.82 ± 18.01 μg/ml), and Lk-6 (36.53 ± 14.42 μg/ml) against D6. Generally, lower activity against W2 was obtained with the most active being LK-4 (24.18±2.50 μg/ml), and Lk-5 (24.42±5.95 μg/ml), while chloroquine (positive control) exerted IC50 of 77.86±4.09 ng/ml (W2) and 15.71±6.49 ng/ml (D6). LK-4 was the most cytotoxic showing cytotoxic concentration (CC50), 46.26 μg/ml. When tested in mice, fractions suppressed Plasmodium berghei significantly compared to the negative control with Lk-3 being most efficacious (80.01±1). Due to substantive efficacy, GC-MS done on Lk-3 revealed 8 compounds where three have previously been ascribed to antimalarial activity and other pharmacological effects. This study adds to present knowledge of antimalarial efficacy of L. kituiensis and provides the basis for further work to be done on the isolation of compounds from its extracts

Benzylation of hydroxy groups with tertiary amine as a base

The benzylation of hydroxy groups in the presence of tertiary amines is described. A mixture of an alcohol and a benzyl halide afforded the corresponding benzyl ether in good to excellent yields in the presence of diisopropylethylamine. The importance of solventless conditions was observed. The reaction showed high tolerance to many functional groups including benzoate, even at a reaction temperature of 150 °C. Sodium iodide was found to be an efficient catalyst to accelerate the reaction

In vitro evaluation of chloroquine-loaded and heparin surface-functionalized solid lipid nanoparticles

Abstract Background Use of chloroquine, an otherwise safe and relatively affordable anti-malarial drug, was discontinued due to widespread prevalence of resistant parasites. Many entrant anti-malarial drugs for treatment of chloroquine resistant malaria raises the concerns of cost and safety among other challenges. Innovative ways of circumventing chloroquine resistance is of paramount importance. Such may include nanoparticulate delivery strategies and targeting. This study evaluated physicochemical properties and in vitro antiplasmodial activity of chloroquine encapsulated heparin functionalized solid lipid nanoparticles (CQ-Hep-SLNs) and non-heparin functionalized SLNs (CQ-SLN) against Plasmodium falciparum. Methods The modified double-emulsion solvent evaporation technique was used to prepare the nanoparticles. HPLC/UV was used to determine the in vitro drug release. The semi-automated micro-dilution technique was adapted in assessing the in vitro antiplasmodial activity to give drug concentration capable of inhibiting 50% of the P. falciparum (IC50), as a function of antiplasmodial efficacy. Results Prepared nanoparticles were below 500 nm in size with % drug loading (%DL) between 21 and 25% and encapsulation efficiency (%EE) of 78–90%. The drug-loaded SLN exhibited a biphasic drug release profile at pH 7.4, with an initial burst release during the first 24 h followed by sustained release in both formulations. Nanoformulated CQ-SLN (4.72 ± 0.14 ng/mL) and CQ-Hep-SLN (2.41 ± 0.27 ng/mL), showed enhanced in vitro antiplasmodial activities against chloroquine sensitive (D6) strain of P. falciparum, albeit with no activity against the chloroquine resistant W2 strain, compared to free CQ standard (5.81 ± 0.18 ng/mL). Conclusions These findings suggest that the nanoformulated drugs displayed enhanced anti-malarial activities against chloroquine sensitive (D6) strains of P. falciparum compared to the free CQ standard. There is some form of potential dual synergistic effect of CQ-loaded heparinized solid lipid nanoparticles (Hep-SLN), meaning that combining heparin and CQ in SLNs has beneficial effects, including potential for specific targeting of parasitized red blood cells as afforded by heparin. Thus, the study has produced SLNs nanoparticles that have superior in vitro activities than CQ on CQ-sensitive parasites