Insights into the role of the cobalt(III)-thiosemicarbazone complex as a potential inhibitor of the Chikungunya virus nsP4.

Chikungunya virus (CHIKV) is the causative agent of chikungunya fever, a disease that can result in disability. Until now, there is no antiviral treatment against CHIKV, demonstrating that there is a need for development of new drugs. Studies have shown that thiosemicarbazones and their metal complexes possess biological activities, and their synthesis is simple, clean, versatile, and results in high yields. Here, we evaluated the mechanism of action (MOA) of a cobalt(III) thiosemicarbazone complex named [CoIII(L1)2]Cl based on its in vitro potent antiviral activity against CHIKV previously evaluated (80% of inhibition on replication). Furthermore, the complex has no toxicity in healthy cells, as confirmed by infecting BHK-21 cells with CHIKV-nanoluciferase in the presence of the compound, showing that [CoIII(L1)2]Cl inhibited CHIKV infection with the selective index of 3.26. [CoIII(L1)2]Cl presented a post-entry effect on viral replication, emphasized by the strong interaction of [CoIII(L1)2]Cl with CHIKV non-structural protein 4 (nsP4) in the microscale thermophoresis assay, suggesting a potential mode of action of this compound against CHIKV. Moreover, in silico analyses by molecular docking demonstrated potential interaction of [CoIII(L1)2]Cl with nsP4 through hydrogen bonds, hydrophobic and electrostatic interactions. The evaluation of ADME-Tox properties showed that [CoIII(L1)2]Cl presents appropriate lipophilicity, good human intestinal absorption, and has no toxicological effect as irritant, mutagenic, reproductive, and tumorigenic side effects.

An In Vivo Assessment of the Effect of Hexane Extract from Endlicheria paniculata Branches and Its Main Compound, Methyldehydrodieugenol B, on Murine Sponge-Induced Inflammation.

The present study aims to explore the anti-inflammatory potential activity of the hexane extract from branches (HEB) of Endlicheria paniculata (Lauraceae) and its main compound, methyldehydrodieugenol B, in the inflammatory response induced by a murine implant sponge model. HPLC-ESI/MS analysis of HEB led to the identification of six chemically related neolignans, with methyldehydrodieugenol B as the main compound. An in silico analysis of the pharmacokinetic parameters of the identified compounds suggested moderate solubility but good absorption and biodistribution in vivo. Thus, the treatment of mice with HEB using in vivo assays indicated that HEB promoted pro-inflammatory, antiangiogenic, and antifibrogenic effects, whereas treatment with methyldehydrodieugenol B caused anti-inflammatory, antifibrogenic, and antiangiogenic effects. The obtained results shown the therapeutic potential of HEB and methyldehydrodieugenol B in the treatment of pathologies associated with inflammation and angiogenesis, including chronic wounds.

Synthesis, molecular properties prediction and cytotoxic screening of 3-(2-aryl-2-oxoethyl)isobenzofuran-1(3H)-ones.

In the present investigation, a collection of nineteen 3-(2-aryl-2-oxoethyl)isobenzofuran-1(3H)-ones was synthesized and screened for their cytotoxic activity against a panel of three leukemia cancer cell lines. The compounds were prepared via ZrOCl2·8H2O catalyzed condensation reactions between phthalaldehydic acid and different acetophenones. The reactions were carried out free of solvent and the isobenzofuran-1(3H)-ones were obtained in good yields (80-92%). The identities of the synthesized compounds were confirmed upon IR and NMR ((1)H and (13)C) spectroscopy as well as high resolution mass spectrometry analyses. Structures of compounds 1, 4 and 16 were also investigated by X-ray analysis. The synthesized compounds were submitted to in vitro bioassays against HL-60, K562 and NALM6 cancer cell lines using MTT cytotoxicity assay. After 48h of treatment, twelve derivatives were able to reduce cell viability and presented IC50 values equal to or below 20µmolL(-1) against at least one of the evaluated lineages. The most active compound corresponded to 3-(3-methylphenyl-2-oxoethyl)isobenzofuran-1(3H)-one (18) (IC50 values obtained for HL-60, K562 and NALM6 were, respectively, 13.5µmolL(-1), 8.83µmolL(-1), and 5.24µmolL(-1)). In addition, compound 18 was capable of triggering apoptosis on NALM6 cells. All isobenzofuranones herein evaluated did not present cytotoxicity on peripheral blood mononuclear cells (PBMC), suggesting selective cytotoxic effect on leukemic cells. A computational study allowed prediction of pharmacokinetics and drug-likeness properties of the synthesized compounds. DFT calculations were performed to obtain the energy values of HOMO, LUMO, and dipole moments of isobenzofuranones.

Zinc-dithiocarbimates for the control of Hemileia vastatrix: a versatile alternative.

BACKGROUND: The purpose of this work was to investigate the potential use of zinc-dithiocarbimate salts to control Hemileia vastatrix, the causal agent of the coffee leaf rust disease, and to evaluate their toxicity towards Apis mellifera, one of the most important coffee plant pollinators. RESULTS: Zinc-dithiocarbimate salts were prepared and fully characterized by infrared, proton (1 H) and carbon-13 (13 C) nuclear magnetic resonance and elemental analyses of carbon (C), hydrogen (H), nitrogen (N) and zinc (Zn). X-ray diffraction technique studies confirmed the proposed structures. The salts inhibited the germination of H. vastatrix spores in vitro, with a 50% inhibitory concentration (IC50 ) from 12 to 18 µmol.L-1 and a 90% inhibitory concentration (IC90 ) from 23 to 26 µmol.L-1 . Zinc-dithiocarbimate salts with the best in vitro results were selected for in vivo experiments with Coffea arabica var Caturra and with the pollinator A. mellifera. The results were similar to those of Mancozeb, a broad-spectrum contact fungicide, with a good control of the disease and low toxicity to the honeybee. CONCLUSION: The zinc-dithiocarbimate complex salts have potential to control coffee leaf rust, with low toxicity to the pollinator insect. © 2022 Society of Chemical Industry.

Dehydrodieugenol B and hexane extract from Endlicheria paniculata regulate inflammation, angiogenesis, and collagen deposition induced by a murine sponge model.

The present study reports the evaluation of hexane extract from Endlicheria paniculata and its main metabolite dehydrodieugenol B in the inflammatory response induced by a murine implant sponge model. As a result, a reduction in the inflammatory markers (myeloperoxidase and N-acetyl-ß-D-glucosaminidase) and number of mast cells were observed in comparison to the control group. All doses were also able to reduce angiogenic parameters evaluated in fibrovascular tissue. In implants treated with dehydrodieugenol B a reduction in total collagen deposition and types I and III collagen fibers were observed, while an increased in total collagen deposition and types I and III collagen fibers were observed in the treatment with hexane extract. Docking studies into cyclooxygenase-2 active site revealed that the dehydrodieugenol B had binding modes and energies comparable with celecoxib, diclofenac and ibuprofen. Therefore, dehydrodieugenol B was able to alter key components of chronic inflammation, resulting in a reduced inflammatory response and also presenting antifibrogenic and antiangiogenic effects. However, treatment with hexane extract resulted in a reduced inflammatory response with antiangiogenic effects, but caused fibrogenic effects.