We have recently reported that a series of 1,3,4-oxadiazol-2-ylbenzenesulfonamides acts as potent and specific monoamine oxidase B (MAO-B) inhibitors with some compounds possessing potencies in the nanomolar range. While sulfonamide compounds (e.g., zonisamide) have been reported to inhibit the MAO enzymes, nanomolar MAO inhibition potencies for this class are not frequently observed. The present study expanded on these findings by replacing the 1,3,4-oxazole moiety with a 1,3-thiazole heterocycle. A series of 23 primary sulfonamides were synthesized by reaction of an α-haloketone with a substituted carbothioamide. The results of the MAO inhibition studies showed that the 1,3-thiazolylbenzenesulfonamides were specific inhibitors of human MAO-B. The most potent MAO-B inhibitor exhibited an in vitro IC50 value of 0.103 µM (3j). The derivatives were, however, weaker inhibitors of human MAO-A with the most potent compound exhibiting an IC50 value of 11.9 µM (3a). Examination of the structure-activity relationships (SARs) showed that the most potent MAO-B inhibition was obtained with substitution of the sulfonamide on the meta position of the phenyl rather than the para position. This study concludes that 1,3-thiazolylbenzenesulfonamides represent a class of potent and specific MAO-B inhibitors, which may serve as leads for the development of new treatments for disease states such as Parkinson’s disease.

In the paper, the effect of voltage increasing (from 500 VDC up to 650 VDC) on the structure and chemical composition of porous coating on titanium made by Plasma Electrolytic Oxidation, is presented. In the present paper, phosphates based coatings enriched with calcium, magnesium, zinc and copper in electrolyte based on 1 L of 85% concentrated H3PO4 with additions of Ca(NO3)2·4H2O, and Mg(NO3)2∙6H2O, and Zn(NO3)2∙6H2O, and Cu(NO3)2∙3H2O, are described. The morphology, chemical and phase composition, are evaluated using SEM, EDS, XRD, XPS, GDOES. Based on all the analyses, it was found out that the PEO coatings are porous and enriched with calcium, magnesium, zinc and copper. They consist mainly of the amorphous phase, which is more visible for higher voltages, and it is correlated with the increasing of the total PEO coating thickness (the higher the voltage, the thicker the PEO coating). However, for 650 VDC an amorphous phase and titanium substrate was also recorded with a signal from Ti2P2O7 crystalline, that was not observed for lower voltages. It was also found out that all the obtained coatings may be divided in three sub-layers, i.e. porous, semiporous, and transition one.

4-(2-Methyloxazol-4-yl)benzenesulfonamide was synthesized by the reaction of 4-(2-bromoacetyl)benzenesulfonamide with an excess of acetamide. The obtained compound was evaluated as a potential inhibitor of human monoamine oxidase (MAO) A and B and was found to inhibit these enzymes with IC50 values of 3.47 μM for MAO-B and 43.3 μM for MAO-A. Thus, the new selective MAO-B inhibitor was identified, which may be used as the lead compound for development anti-Parkinson’s disease agents.

3-(3,4-Dichlorophenyl)-5-(1H-indol-5-yl)-1,2,4-oxadiazole was synthesized via the condensation of 3,4-dichlorobenzamidoxime and methyl 1H-indole-5-carboxylate using superbasic medium (NaOH/DMSO). The compound was tested as a potential inhibitor of human monoamine oxidase (MAO) A and B. It demonstrated notable inhibition with an IC50 value of 0.036 μM for MAO-B and isoform specificity. The product was characterized by 1H NMR, 13C NMR, and HRMS. In conclusion, the new active MAO-B inhibitor may serve as a candidate for the future discovery of therapeutic agents for neurodegenerative disorders such as Parkinson’s disease.

This study explores the potential of natural compounds, including Daidzin, Luteolin, and Silibinin, as inhibitors of human monoamine oxidase B (MAO-B) for the treatment of Parkinson's disease. Docking simulations were performed using Autodock Vina with Pyrx program to evaluate the binding affinities of these compounds with MAO-B. Results indicate that Daidzin, Luteolin, and Silibinin exhibit promising binding affinities with MAO-B, with Daidzin demonstrating the highest affinity. Toxicity parameters were further predicted using the PkCSM Server, confirming the low toxicity of these compounds. Overall, the findings suggest that Daidzin, Luteolin, and Silibinin have the potential to be effective and safe treatments for Parkinson's disease through their inhibition of MAO-B. Further experimental validation is warranted to support their therapeutic efficacy in clinical settings.

Alzheimer's disease is a multifactorial neurodegenerative disorder, with Acetylcholinesterase, Butyrylcholinesterase, Beta secretase, Glycogen Synthase Kinase beta and Monoamine oxidase B playing central role in it's pathogenesis. Therefore, this research aims to discover potential curative multitarget drugs derived from African natural products capable of addressing the multifactorial characteristics of the disease. In silico approaches were used to filter a 880 african natural compounds library based on selected pharmacokinetic properties. Molecular docking against the five aforementioned proteins, followed by Molecular Mechanics with Generalised Born and Surface Area Solvation scoring for the top compounds were used to assess binding. Density Functional Theory studies were used to assess electronic transitions. Pharmacokinetic filters resulted in 200 compounds, of which only five were selected after molecular docking. Density Functional Theory and Molecular Mechanics with Generalised Born and Surface Area Solvation scoring resulted in 3 potential multitarget compounds. Compound 157 (ZINC000095485950) showed triple-target inhibitory activity against Butyrylcholinesterase, Glycogen Synthase Kinase beta and Beta-secretase, while compounds 159 (ZINC000095485952) and 696 (ZINC000039144622) showed dual-target inhibitory activity against Butyrylcholinesterase and Glycogen Synthase Kinase beta. Molecular dynamics simulation and further experimental assessments are suggested.

Keywords: Pulp cell, Periodontal cell, Micro-Arc Oxidation (MAO), Sever Plastic deformation (SPD), Equal Channel Angular Pressing (ECAP), AlamarBlue, ELISA, trypsin