Structure and Ligand Based Virtual Screening and MPO Topological Analysis of Triazolo Thiadiazepine-fused Coumarin Derivatives as Anti-Parkinson Drug Candidates.

Parkinson's disease (PD) is a debilitating condition that can cause locomotor problems in affected patients, such as tremors and body rigidity. PD therapy often includes the use of monoamine oxidase B (MAOB) inhibitors, particularly phenylhalogen compounds and coumarin-based semi-synthetic compounds. The objective of this study was to analyze the structural, pharmacokinetic, and pharmacodynamic profile of a series of Triazolo Thiadiazepine-fused Coumarin Derivatives (TDCDs) against MAOB, in comparison with the inhibitor safinamide. To achieve this goal, we utilized structure-based virtual screening techniques, including target prediction and absorption, distribution, metabolism, and excretion (ADME) prediction based on multi-parameter optimization (MPO) topological analysis, as well as ligand-based virtual screening techniques, such as docking and molecular dynamics. The findings indicate that the TDCDs exhibit structural similarity to other bioactive compounds containing coumarin and MAOB-binding azoles, which are present in the ChEMBL database. The topological analyses suggest that TDCD3 has the best ADME profile, particularly due to the alignment between low lipophilicity and high polarity. The coumarin and triazole portions make a strong contribution to this profile, resulting in a permeability with Papp estimated at 2.15 × 10-5 cm/s, indicating high cell viability. The substance is predicted to be metabolically stable. It is important to note that this is an objective evaluation based on the available data. Molecular docking simulations showed that the ligand has an affinity energy of - 8.075 kcal/mol with MAOB and interacts with biological substrate residues such as Pro102 and Phe103. The results suggest that the compound has a safe profile in relation to the MAOB model, making it a promising active ingredient for the treatment of PD.

Antibacterial effectiveness of trans-cinnamaldehyde against foodborne Enterobacteriaceae and its adjuvant effect with gentamicin.

The Enterobacteriaceae family is recognized as a primary group of Gram-negative pathogens responsible for foodborne illnesses and is frequently associated with antibiotic resistance. The present study explores the natural-based compound trans-cinnamaldehyde (TC) against drug-resistant Enterobacteriaceae and its synergism with gentamicin (GEN) to address this issue. The research employs three strains of Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae, previously isolated from shrimp. The antibacterial activity was evaluated by the disk diffusion method, microdilution test, kinetics of growth, and time-kill curve. In addition, the synergistic effect between TC/GEN was investigated by checkerboard assay. All strains showed sensitivity to TC with an inhibition zone diameter > 35 mm. The TC showed inhibitory and bactericidal action in the most tested bacteria around 625 µg/mL. Sub-inhibitory amounts (1/2 and 1/4 MIC) of TC interfered with the growth kinetics by lag phase extension and decreased the log phase. Time-kill curves show a reduction of viable cells after the first hour of TC treatment at bactericidal concentrations. The synergistic effect between TC/GEN was observed for E. coli and E. cloacae strains with FICi ranging from 0.15 to 0.50. These findings, therefore, suggest TC as a promising alternative in the fight against drug-resistant Enterobacteriaceae that can cause foodborne illnesses.

Enhancement of chlorhexidine activity against planktonic and biofilm forms of oral streptococci by two Croton spp. essential oils from the Caatinga biome.

This work investigates the ability of two Croton spp. essential oils (EO) to enhance chlorhexidine (CHX) activity against oral streptococci. EO's chemical composition of Croton argyrophyllus and C. pluriglandulosus was determined by GC-MS/FID. The microbial growth kinetics and minimum inhibitory concentration (MIC) of EOs and CHX were determined, followed by their synergism against S. mutans UA159 and ATCC 25175, S. salivarius ATCC 7073 and S. sp. ATCC 15300. The microplate-based method was used to determine the EO/CHX activity against 24-h-old biofilms. The major compounds were α-pinene (54.74%) and bicyclogermacrene (16.08%) for EOAr and 1,8-cineole (17.41%), methyleugenol (16.06%) and elemicin (15.99%) for EOPg. Both EO had MIC around 16,000 µg/mL. EOs/CHX presented a synergistic effect against most strains (FICi from 0.133 to 0.375), and OE/CHX-treated biofilms showed a reduction in biomass and cell viability compared to CHX, only (p < 0.01). Thus, the EOs works as natural adjuvants for CHX.