Synthesis, Characterization, and Biological Activity of Water-Soluble, Dual Anionic and Cationic Ruthenium-Arene Complexes Bearing Imidazol(in)ium-2-dithiocarboxylate Ligands.

An efficient synthetic protocol was devised for the preparation of five cationic ruthenium-arene complexes bearing imidazol(in)ium-2-dithiocarboxylate ligands from the [RuCl2(p-cymene)]2 dimer and 2 equiv of an NHC·CS2 zwitterion. The reactions proceeded cleanly and swiftly in dichloromethane at room temperature to afford the expected [RuCl(p-cymene)(S2C·NHC)]Cl products in quantitative yields. When the [RuCl2(p-cymene)]2 dimer was reacted with only 1 equiv of a dithiolate betaine under the same experimental conditions, a set of five bimetallic compounds with the generic formula [RuCl(p-cymene)(S2C·NHC)][RuCl3(p-cymene)] was obtained in quantitative yields. These novel, dual anionic and cationic ruthenium-arene complexes were fully characterized by various analytical techniques. NMR titrations showed that the chelation of the dithiocarboxylate ligands to afford [RuCl(p-cymene)(S2C·NHC)]+ cations was quantitative and irreversible. Conversely, the formation of the [RuCl3(p-cymene)]- anion was limited by an equilibrium, and this species readily dissociated into Cl- anions and the [RuCl2(p-cymene)]2 dimer. The position of the equilibrium was strongly influenced by the nature of the solvent and was rather insensitive to the temperature. Two monometallic and two bimetallic complexes cocrystallized with water, and their molecular structures were solved by X-ray diffraction analysis. Crystallography revealed the existence of strong interactions between the azolium ring protons of the cationic complexes and neighboring donor groups from the anions or the solvent. The various compounds under investigation were highly soluble in water. They were all strongly cytotoxic against K562 cancer cells. Furthermore, with a selectivity index of 32.1, the [RuCl(p-cymene)(S2C·SIDip)]Cl complex remarkably targeted the erythroleukemic cells vs mouse splenocytes.

In Vitro Antiplasmodial and Cytotoxic Activities of Compounds from the Roots of Eriosema montanum Baker f. (Fabaceae).

Malaria remains one of the leading causes of death in sub-Saharan Africa, ranked in the top three infectious diseases in the world. Plants of the Eriosema genus have been reported to be used for the treatment of this disease, but scientific evidence is still missing for some of them. In the present study, the in vitro antiplasmodial activity of the crude extract and compounds from Eriosema montanum Baker f. roots were tested against the 3D7 strain of Plasmodium falciparum and revealed using the SYBR Green, a DNA intercalating compound. The cytotoxicity effect of the compounds on a human cancer cell line (THP-1) was assessed to determine their selectivity index. It was found that the crude extract of the plant displayed a significant antiplasmodial activity with an IC50 (µg/mL) = 17.68 ± 4.030 and a cytotoxic activity with a CC50 (µg/mL) = 101.5 ± 12.6, corresponding to a selective antiplasmodial activity of 5.7. Bioactivity-guided isolation of the major compounds of the roots' crude extract afforded seven compounds, including genistein, genistin and eucomic acid. Under our experimental conditions, using Artemisinin as a positive control, eucomic acid showed the best inhibitory activity against the P. falciparum 3D7, a well-known chloroquine-sensitive strain. The present results provide a referential basis to support the traditional use of Eriosema species in the treatment of malaria.

The Inhibition of NLRP3 Inflammasome and IL-6 Production by Hibiscus noldeae Baker f. Derived Constituents Provides a Link to Its Anti-Inflammatory Therapeutic Potentials.

The activation of NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome and/or its components is associated with the physio-pathogenesis of many respiratory diseases including asthma, COPD (chronic obstructive pulmonary disease), SARS Cov-2 (severe acute respiratory syndrome coronavirus 2), and in several autoimmune diseases. Hibiscus noldeae Baker f. has been widely reported to be traditionally used in the treatment of different ailments, some of which are of inflammatory background such as asthma, wounds, headache, etc. However, the claims have not been supported by evidence at the molecular and functional levels. Here, we report on the bio-guided fractionation of H. noldeae and assessment of the inhibitory properties of some fractions and purified compounds on NLRP3 inflammasome and Interleukin 6 (IL-6). The activation of the NLRP3 inflammasome was determined by detecting the activity of caspase-1 and the production of Interleukin 1ß (IL-1ß) in Lipopolysaccharide (LPS) and ATP-stimulated Tamm-Horsfall Protein 1 (THP-1) macrophages, while the production of IL-6 was studied in LPS-stimulated RAW264.7 mouse macrophages. It was observed that hexane and ethyl acetate fractions of the crude extract of the aerial parts of H. noldeae, as well as caffeic acid, isoquercetin, and ER2.4 and ER2.7 fractions revealed significant inhibitory effects on Caspase-1 activities, and on IL-1ß and IL-6 production. The ER2.4 and ER2.7 fractions downregulated the production of IL-1ß and IL-6, in a similar range as the caspase-1 inhibitor AC-YVAD-CHO and the drug Dexamethasone, both used as controls, respectively. Overall, our work does provide the very first scientific based evidence for Hibiscus noldeae anti-inflammatory effects and widespread use by traditional healers in Rwanda for a variety of ailments.

An ethnobotanical survey and inhibitory effects on NLRP3 inflammasomes/Caspase-1 of herbal recipes' extracts traditionally used in Rwanda for asthma treatment.

ETHNOPHARMACOLOGICAL RELEVANCE: Respiratory diseases and asthma, in particular, are nowadays a global health problem. In Rwanda, some traditional healers claim to treat asthma with plant-based recipes, though there is no scientific proof so far. AIM OF THE STUDY: Our study aimed at evaluating the toxicity and the anti-inflammatory effect of plant recipes used in Rwanda against asthma in order to select potential candidates for further characterization of the active compounds. MATERIALS AND METHODS: Water (aqueous) and methanol-dichloromethane (organic) extracts from selected folkloric recipes were submitted for toxicity test on THP-1 derived macrophages using CellTiter-Glo Luminescent Cell Viability Assay. The evaluation of the anti-inflammatory effect of the plant extracts was carried out using the Caspase-Glo 1 Inflammasome assay on THP-1 -derived macrophages. RESULTS: Most of both organic and aqueous extract showed more than 95% of cell viability up to 200 µg/ml, except for R03Cn organic extract that inhibited 25% of the cell viability. Plant extracts inhibited caspase-1 activation in THP-1 derived macrophages in a dose-dependent manner. Four extracts (R03Cn and R07Kn aqueous extracts, R10MK and R19Sz organic extracts) strongly downregulated the activation of caspase-1 (more than 70% at 50 µg/ml). In general, organic extracts exhibited better caspase-1 inhibitory effects than their aqueous counterparts. CONCLUSIONS: The inhibition of inflammasome/caspase-1 is one of key mechanisms of action in asthma. Some traditional recipes are active on this mechanism and are thus strong candidates for the treatment of asthma and other inflammasome-mediated diseases. Further investigations are needed to characterize active molecules.