Insights for the Next Generation of Ketamine for the Treatment of Depressive Disorder.

Treatment-resistant depression responds quickly to ketamine. As an -methyl-d-aspartate receptor (NMDAR) antagonist, ketamine may affect prefrontal cortex (PFC) neurons. Recent investigations reveal that the ()-enantiomer is the most effective and least abuseable antidepressant.

Investigation of antibacterial mode of action of ω-aminoalkoxylxanthones by NMR-based metabolomics and molecular docking.

Introduction: The knowledge of the mode of action of an antimicrobial is essential for drug development and helps to fight against bacterial resistance. Thus, it is crucial to use analytical techniques to study the mechanism of action of substances that have potential to act as antibacterial agents OBJECTIVE: To use NMR-based metabolomics combined with chemometrics and molecular docking to identify the metabolic responses of Staphylococcus aureus following exposure to commercial antibiotics and some synthesized ω-aminoalkoxylxanthones.

Methods: Intracellular metabolites of S.

Cardiovascular-kidney-metabolic syndrome - An integrative review.

The American Heart Association recently defined the complex interactions among the cardiovascular, renal, and metabolic systems as CKM syndrome. To promote better patient outcomes, having a more profound understanding of CKM pathophysiology and pursuing holistic preventative and therapy strategies is critical. Despite many gaps in understanding CKM syndrome, this study attempts to elucidate two of these gaps: the new emerging biomarkers for screening and the role of inflammation in its pathophysiology.

Supplementation of high doses of vitamin D during the gestational period do not cause reproductive, teratogenic and genotoxic damage in mice.

Vitamin D deficiency during pregnancy may have adverse effects on embryo-fetal and postnatal development. Indeed, vitamin D supplementation has been indicated for pregnant women. However, there are no studies that indicate the safe dose of this supplementation during the gestational period.

Cardioprotective Effects of DC. in Nicotine-Treated Hypertensive Rats.

DC. (Asteraceae), "arnica brasileira," is a Brazilian species popularly used to treat hypertension or renal ailments. This study investigated the cardioprotective effects of standardized extract (EESM) in nicotine-treated spontaneously hypertensive rats (SHRs).

Exploring microalgal and cyanobacterial metabolites with antiprotozoal activity against Leishmania and Trypanosoma parasites.

Neglected tropical diseases (NTD) like Leishmaniasis and trypanosomiasis affect millions of people annually, while currently used antiprotozoal drugs have serious side effects. Drug research based on natural products has shown that microalgae and cyanobacteria are a promising platform of biochemically active compounds with antiprotozoal activity. These unicellular photosynthetic organisms are rich in polyunsaturated fatty acids, pigments including phycocyanin, chlorophylls and carotenoids, polyphenols, bioactive peptides, terpenes, alkaloids, which have proven antioxidant, antimicrobial, antiviral, antiplasmodial and antiprotozoal properties.

Bridging the Gap: Exploring the Preclinical Potential of in Metabolic-Associated Fatty Liver Disease.

Metabolic-associated fatty liver disease (MAFLD) is a complex condition characterized by steatosis and metabolic disturbances. Risk factors such as diabetes, cigarette smoking, and dyslipidaemia contribute to its development and progression. Effective and safe therapies for MAFLD are urgently needed.

S100s and HMGB1 Crosstalk in Pancreatic Cancer Tumors.

Pancreatic cancer remains a disease that is very difficult to treat. S100 proteins are small calcium binding proteins with diverse intra- and extracellular functions that modulate different aspects of tumorigenesis, including tumor growth and metastasis. High mobility group box 1 (HMGB1) protein is a multifaceted protein that also actively influences the development and progression of tumors.

The ethanolic extract of Salvia lachnostachys Benth is not maternotoxic, does not alter reproductive performance, but has teratogenic potential.

Salvia lachnostachys Benth is native to Brazil and has anti-inflammatory, anti-arthritic, cytotoxic, antitumor, and antihyperalgesic activities. The population, including pregnant women, consume this plant to treat pain, inflammation, flu, spasms, insomnia, and depression, mainly. There are no safety reports on the use of this plant during pregnancy.

The Ethanolic Extract of Kunth Is Teratogenic and Interferes with the Ossification Process of Swiss Mice Fetuses.

Kunth is a plant traditionally used to treat pain and inflammation in the Mato Grosso do Sul, Brazil. Even pregnant women consume this plant. Toxicology studies of the ethanolic extract from the leaves of (EEPg) could establish the safety of popular use of .

3-Heptylidene-4,6-Dimethoxy-3-Isobenzofuran-1-One Is Genotoxic, Increases the Frequency of Cell Death, and Potentiates the Effects of Cyclophosphamide and Cisplatin.

3-heptylidene-4,6-dimethoxy-3-isobenzofuran-1-one (Phthalide ) is the precursor of three resorcinol lipids that have been described as potential chemotherapeutic agents and capable of potentiating the effects of cyclophosphamide. In this study, we evaluated the genotoxic potential, cell-killing potential, and interactions with cyclophosphamide and cisplatin of phthalide . Twelve groups were created from 120 mice: Negative Control, cyclophosphamide (100 mg/kg), cisplatin (6 mg/kg), Phthalide (5, 10 and 20 mg/kg), and associations of with cyclophosphamide and with cisplatin.

ZIM, a Norbornene Derived from 4-Aminoantipyrine, Induces DNA Damage and Cell Death but in Association Reduces the Effect of Commercial Chemotherapeutics.

Cancer incidence is increasing, and the drugs are not very selective. These drugs cause adverse effects, and the cells become resistant. Therefore, new drugs are needed.

The Ethanolic Extract of Mart. Does Not Alter Reproductive Performance or Embryo-Fetal Development, nor Does It Cause Chromosomal Damage.

is a native Brazilian plant found in the State of Mato Grosso do Sul. It is used in folk medicine to treat kidney diseases, skin diseases, infections, rheumatism, gastrointestinal diseases, and respiratory diseases. It is also used as an abortifacient.

Design, synthesis and in vivo evaluation of 1,4-dioxo-2-butenyl aryl amine derivatives as a promising anti-inflammatory drug prototype.

Inflammation is a natural response of the organism to an infection, trauma, or cellular stress. Pain is the first symptom of acute and chronic inflammation. The standard class of medication to treat inflammatory pain is the nonsteroidal anti-inflammatory drug (NSAID).

Sulphonates' mixtures and emulsions obtained from technical cashew nut shell liquid and cardanol for control of Aedes aegypti (Diptera: Culicidae).

Aedes aegypti is the main mosquito vector of dengue, zika, chikungunya, and yellow fever diseases. The low effectiveness of vector control options is mainly related to the increased insect's resistance and to the toxicity of products used for non-target organisms. The development of new environmentally friendly and safer products is imperative.

A Method for the Catalytic Enantioselective Synthesis of Chiral α-Azido and α-Amino Ketones from Racemic α-Bromo Ketones, and Its Generalization to the Formation of Bonds to C, O, and S.

A new and practical method has been developed for the transformation of racemic α-bromo ketones to chiral α-azido and α-amino ketones with high enantioselectivity using phase transfer, ion-pair mediated reactions with a recoverable chiral quaternary salt (10 mol %) as catalyst in fluorobenzene-water. The process has been generalized to a variety of other attachments including of C, O, S, and NHR.

Biomonitoring of pharmacists and nurses at occupational risk from handling antineoplastic agents.

Objective: The objective of this study was to evaluate the frequency of genetic lesions in pharmacists and nurses who prepare and/or handle antineoplastic agents and to evaluate whether there are traces of contaminants in the urine of these professionals.

Methods: A total of 59 professionals participated in the study, of which 10 were non-exposed professionals (controls), 25 were pharmacists, and 24 were nurses.

Key Findings: There was a significant increase in genetic damage in lymphocytes and cells of the oral mucosa in both pharmacists and nurses.

Assessment of the toxicogenic effects and cell death potential of the ester (Z)-methyl 4-((1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)amino)-4-oxobut-2-anoate in combination with cisplatin, cyclophosphamide and doxorubicin.

Despite rapid advances in both the early detection and treatment of cancer, the mortality from this disease remains high, which justifies the development of new products that are more selective and effective and have fewer side effects. Accordingly, a novel ester was synthesized that contains two pharmacophores with important biological activities: (I) 4-aminoantipyrine, which has anti-inflammatory and antioxidant effects, and (II) the pharmacophore 1,4-dioxo-butenyl, which has cytotoxic activity. When administered alone, this compound is non-genotoxic, and it does not cause an increasing in splenic phagocytosis.

Synthesis of Chiral Cyclic Alcohols from Chiral Epoxides by H or N Substitution with Frontside Displacement.

Diverse examples are provided of enantioselective sequences for the transformation of cycloalkenes to either chiral trans-β-substituted cycloalkanols or chiral α-amino ketones.

Resorcinolic lipid 3-heptyl-3,4,6-trimethoxy-3H-isobenzofuran-1-one is a strategy for melanoma treatment.

Aims: Previous studies performed by our research group indicated that cytosporone analogues are capable of prevent or repair DNA damages. This work presents the evaluation of the activity of AMS35AA for metastatic murine melanoma cells (B16F10) in experimental model in vitro and, in pre-clinic assay of metastatic melanoma in vivo, using mice lineage C57BL/6.

Main Methods: In vitro assays were performed: MTT and comet assay, flow cytometry evaluation, gene expression assay by RT-PCR, qualitative evaluation of cell death using B16F10 cells.

New Bis copper complex ((Z) -4 - ((4-chlorophenyl) amino) -4-oxobut-2-enoyl) oxy): Cytotoxicity in 4T1 cells and their toxicogenic potential in Swiss mice.

Copper (II) complexes are promising in the development of new synthetic models for cancer treatment. In this context, we synthesized a new copper complex containing the pharmacophore group 1,4-dioxo-2-butenyl, the Bis(((Z)-4-((4-chlorophenyl) amino)-4-oxobut-2-enoyl)oxy) copper compound and we evaluated its antitumor activity in 4 T1 murine mammary adenocarcinoma cells and their toxicogenic effect in Swiss mice. The compound demonstrated cytotoxicity and genotoxicity to 4 T1 cells, and after cell cycle arrest in G1, which occurred by the increase in ATM and p21 expression, it induced the cells to apoptosis by increasing BAX and caspase-7.

Evaluation of the Antitumor Potential of the Resorcinolic Lipid 3-Heptyl-3,4,6-trimethoxy-3H-isobenzofuran-1-one in Breast Cancer Cells.

Background/aim: In recent years, the search for new anticancer experimental agents derived from natural products or synthetic analogues, such as resorcinolic lipids, has received increased attention. The present study aimed to evaluate the antitumor potential, describe the cell death mechanism and the effects of 3-Heptyl-3,4,6-trimethoxy-3Hisobenzofuran-1-one (AMS35AA) in combination with different chemotherapeutic agents in the MCF-7 cell line.

Materials And Methods: Analysis of cytotoxic, genotoxic, membrane integrity, cell death and gene expression induced by the compound was performed.

Assessment of genetic integrity, splenic phagocytosis and cell death potential of (Z)-4-((1,5-dimethyl-3-oxo-2-phenyl-2,3dihydro-1H-pyrazol-4-yl) amino)-4-oxobut-2-enoic acid and its effect when combined with commercial chemotherapeutics.

The increased incidence of cancer and its high treatment costs have encouraged the search for new compounds to be used in adjuvant therapies for this disease. This study discloses the synthesis of (Z)-4-((1,5-dimethyl-3-oxo-2-phenyl-2,3dihydro-1H-pyrazol-4-yl) amino)-4-oxobut-2-enoic acid (IR-01) and evaluates not only the action of this compound on genetic integrity, increase in splenic phagocytosis and induction of cell death but also its effects in combination with the commercial chemotherapeutic agents doxorubicin, cisplatin and cyclophosphamide. IR-01 was designed and synthesized based on two multifunctionalyzed structural fragments: 4-aminoantipyrine, an active dipyrone metabolite, described as an antioxidant and anti-inflammatory agent; and the pharmacophore fragment 1,4-dioxo-2-butenyl, a cytotoxic agent.