Inhibitors of Farnesyl Diphosphate Synthase and Squalene Synthase: Potential Source for Anti-<i>Trypanosomatidae</i> Drug Discovery

Trypanosomatids are mainly responsible for leishmaniasis, sleeping sickness, and Chagas disease, which are the most challenging among the neglected tropical diseases due to the problem of drug resistance. Although problems of target deconvolution and polypharmacology are encountered, a target-based approach is a rational method for screening drug candidates targeting a biomolecule that causes infections. The present study aims to summarize the latest information regarding potential inhibitors of squalene synthase and farnesyl phosphate synthase with anti-Trypanosomatidae activity. The information was obtained by referencing textbooks and major scientific databases from their inception until April 2023. Based on in vitro experiments, more than seventy compounds were reported to inhibit squalene synthase and farnesyl diphosphate synthase. Among these compounds, more than 30 were found to be active in vitro against Trypanosomatidae, inferring that these compounds can be used as scaffolds to develop new drugs against trypanosomatid-related infections. Overall, natural and synthetic products can inhibit enzymes that are crucial for the survival and virulence of trypanosomatids. Moreover, in vitro experiments have confirmed the activity of more than half of these inhibitors using cell-based assays. Nevertheless, additional studies on the cytotoxicity, pharmacokinetics, and lead optimization of potent anti-Trypanosomatid compounds should be investigated

In Situ Stabilisation of Silver Nanoparticles at Chitosan-Functionalised Graphene Oxide for Reduction of 2,4-Dinitrophenol in Water

This investigation reports the in situ growth of silver nanoparticles onto covalently bonded graphene oxide-chitosan, which serve as supported nanocatalysts for the NaBH4 reduction of 2,4-dinitrophenol in aqueous systems. Fumaryl chloride reacted with chitosan in an acidic environment to yield a tailored polymeric material. The latter was, in turn, treated with the pre-synthesised graphene oxide sheets under acidic conditions to generate the GO-functionalised membrane (GO-FL-CS). The adsorption of Ag+ from aqueous media by GO-FL-CS yielded a set of membranes that were decorated with silver nanoparticles (Ag NPs@GO-FL-CS) without any reducing agent. Various analytical tools were used to characterise these composites, including Fourier transform infrared spectroscopy, Brunauer-Emmett-Teller surface area analysis, X-ray diffraction, scanning electron microscopy/energy-dispersive X-ray analysis, inductively coupled plasma-mass spectrometry, and transmission electron microscopy. The silver-loaded materials were further used for the remediation of 2,4-dinitrophenol from aqueous solutions under batch operation. The BET analysis revealed that the functionalisation of GO with chitosan and Ag NPs (average size 20–60 nm) resulted in a three-fold increased surface area. The optimised catalyst (Ag mass loading 16.95%) displayed remarkable activity with an apparent pseudo-first-order rate constant of 13.5 × 10−3 min−1. The cyclic voltammetry experiment was conducted to determine the nitro-conversion pathway. The reusability/stability test showed no significant reduction efficiency of this metal-laden composite over six cycles. Findings from the study revealed that Ag NPs@GO-FL-CS could be employed as a low-cost and recyclable catalyst to convert toxic nitroaromatics in wastewater

TiO2 assisted photocatalysts for degradation of emerging organic pollutants in water and wastewater

International audienc

Characterization of Slaughterhouse Wastewater and Development of Treatment Techniques: A Review

International audienceCommercialization in the meat-processing industry has emerged as one of the major agrobusiness challenges due to the large volume of wastewater produced during slaughtering and cleaning of slaughtering facilities. Slaughterhouse wastewater (SWW) contains proteins, fats, high organic contents, microbes, and other emerging pollutants (pharmaceutical and veterinary residues). It is important to first characterize the wastewater so that adequate treatment techniques can be employed so that discharge of this wastewater does not negatively impact the environment. Conventional characterization bulk parameters of slaughterhouse wastewater include pH, color, turbidity, biochemical oxygen demand (BOD), chemical oxygen demand (COD), total organic carbon (TOC), total suspended solids (TSS), total nitrogen (TN), total phosphorus (TP), and coliform counts. Characterization studies conducted have revealed the effects of the pollutants on microbial activity of SWW through identification of toxicity of antibiotic-resistant strains of bacteria. Due to the high-strength characteristics and complex recalcitrant pollutants, treatment techniques through combined processes such as anaerobic digestion coupled with advanced oxidation process were found to be more effective than stand-alone methods. Hence, there is need to explore and evaluate innovative treatments and techniques to provide a comprehensive summary of processes that can reduce the toxicity of slaughterhouse wastewater to the environment. This work presents a review of recent studies on the characterization of SWW, innovative treatments and technologies, and critical assessment for future research

Membrane stabilisation: a possible anti-inflammatory mechanism for the extracts and compounds from <i>Spathodea campanulata</i>

<div><p>This study was undertaken to evaluate the efficiency of extract, fractions and pure molecules from <i>Spathodea campanulata</i> (SC) towards inflammation. Polarity-based extracts of SC were found active in stabilising red blood cell (RBC) membrane indicating anti-inflammatory potential. Bioactivity-guided isolation of SC produced 1-<i>O</i>-(<i>E</i>)-caffeoyl-β-gentiobiose and (2<i>S</i>)-1,2-di-<i>O</i>-[(9<i>Z</i>,12<i>Z</i>,15<i>Z</i>)-octadeca-9,12,15-trienoyl]-3-<i>O</i>-[α-d-galctopyranosyl-(1″ → 6′)-<i>O</i>-β-d-galactopyranosyl] glycerol as the active constituents with 65.91% and 67.41% of membrane stability, respectively. Activity of the third compound (verminoside) could not be ascertained owing to extremely low recoverability. Furthermore, the isolated compounds were subjected to <i>in silico</i> studies. The compounds showed good binding affinity towards cyclooxygenase-2. Absorption, distribution, metabolism & excretion (ADME)-toxicity studies illustrated that the isolated compounds are free of toxicity. These observations help us to conclude that SC might exert its anti-inflammatory activity by soothing the RBC membrane as it is the case for non-steroidal anti-inflammatory drugs towards lysozomal membranes. Therefore, SC might be considered as a potential candidate for development of anti-inflammatory drugs.</p></div

RP-HPLC-DAD method for the identification of two potential antioxidant agents namely verminoside and 1-<i>O</i>-(<i>E</i>)-caffeoyl-β-gentiobiose from <i>Spathodea campanulata</i> leaves

<div><p>A simple and reliable high-performance liquid chromatographic method was successfully developed for the study of fingerprint chromatograms of extract and fractions from the leaves of <i>Spathodea campanulata</i> (SC) using verminoside (<b>1</b>) and 1-<i>O</i>-(<i>E</i>)-caffeoyl-β-gentiobiose (<b>2</b>) as marker compounds. Antioxidant activity of SC was determined by using free radical of 2,2-diphenyl-1-picryl-hydrazyl-hydrate as an experimental model. The docking study of selected target, tyrosinase and ligands (ascorbic acid, compounds <b>1</b> and <b>2</b>) was performed through Autodock Vina v0.8. Fingerprints of methanol, chloroform, ethylacetate, <i>n</i>-butanol and water extracts could resolve 13, 11, 22, 16 and 5 peaks, respectively. Extract, fractions and compounds <b>1</b> and <b>2</b> previously isolated from SC displayed remarkable antioxidant activity with radical-scavenging activity ranging from 2.5 to 6.7 μg/mL. <i>In silico</i> study identified compounds <b>1</b> and <b>2</b> as potential inhibitors of tyrosinase correlating with the observed antioxidant activity <i>in vitro</i>.</p></div