Synthesis and Evaluation of 3-Halobenzo[b]thiophenes as Potential Antibacterial and Antifungal Agents

The global health concern of antimicrobial resistance has harnessed research interest to find new classes of antibiotics to combat disease-causing pathogens. In our studies, 3-halobenzo[b]thiophene derivatives were synthesized and tested for their antimicrobial activities using the broth microdilution susceptibility method. The 3-halo substituted benzo[b]thiophenes were synthesized starting from 2-alkynyl thioanisoles using a convenient electrophilic cyclization methodology that utilizes sodium halides as the source of electrophilic halogens when reacted along with copper(II) sulfate. This environmentally benign methodology is facile, uses ethanol as the solvent, and results in 3-halo substituted benzo[b]thiophene structures in very high yields. The cyclohexanol-substituted 3-chloro and 3-bromobenzo[b]thiophenes resulted in a low MIC of 16 µg/mL against Gram-positive bacteria and yeast. Additionally, in silico absorption, distribution, metabolism, and excretion (ADME) properties of the compounds were determined. The compounds with the lowest MIC values showed excellent drug-like properties with no violations to Lipinski, Veber, and Muegge filters. The time-kill curve was obtained for cyclohexanol-substituted 3-chlorobenzo[b]thiophenes against Staphylococcus aureus, which showed fast bactericidal activity at MIC.

Efficient Electrocatalytic Approach to Spiro[Furo[3,2-b]pyran-2,5′-pyrimidine] Scaffold as Inhibitor of Aldose Reductase

A continuously growing interest in convenient and ‘green’ reaction techniques encourages organic chemists to elaborate on new synthetic methodologies. Nowadays, organic electrochemistry is a new useful method with important synthetic and ecological advantages. The employment of an electrocatalytic methodology in cascade reactions is very promising because it provides the combination of the synthetic virtues of the cascade strategy with the ecological benefits and convenience of electrocatalytic procedures. In this research, a new type of the electrocatalytic cascade transformation was found: the electrochemical cyclization of 1,3-dimethyl-5-[[3-hydroxy-6-(hydroxymethyl)-4-oxo-4H-pyran-2-yl](aryl)methyl]pyrimidine-2,4,6(1H,3H,5H)-triones was carried out in alcohols in an undivided cell in the presence of sodium halides with the selective formation of spiro[furo[3,2-b]pyran-2,5′-pyrimidines] in 59-95% yields. This new electrocatalytic process is a selective, facile, and efficient way to create spiro[furo[3,2-b]pyran-2,5′-pyrimidines], which are pharmacologically active heterocyclic systems with different biomedical applications. Spiro[furo[3,2-b]pyran-2,5′-pyrimidines] were found to occupy the binding pocket of aldose reductase and inhibit it. The values of the binding energy and Lead Finder’s Virtual Screening scoring function showed that the formation of protein–ligand complexes was favorable. The synthesized compounds are promising for the inhibition of aldose reductase. This makes them interesting for study in the treatment of diabetes or similar diseases.

Ceftriaxone Degradation in the Presence of Sodium Halides Investigated by Electrochemical Methods Assisted by UV-Vis Spectrophotometry

The electrochemical stability of ceftriaxone (CFTX), belonging to the third generation of cephalosporin antibiotics, was studied by electrochemical measurements recorded on a platinum electrode (Pt) in aqueous solutions containing sodium halides. The electrochemical behavior of ceftriaxone was investigated by cyclic voltammetry (CV) and constant current density electrolysis assisted by UV-Vis spectrophotometry. Cyclic voltammetry highlighted that the addition of CFTX in sodium halide solutions leads to significant changes in the hysteresis characteristics due to specific interactions with active species from electrolytes, as well as with the platinum electrode surface. After CV, when an exterior electric stimulus in short time (40 s) was applied, the UV-Vis spectra illustrated that CFTX is stable in the presence of F− ions, it is electro(degraded/transformed) in the presence of Cl− and Br− ions and interacts instantly with I− species. Electrolysis at constant current density confirms the results obtained from cyclic voltammetry, showing that (i) in the presence of fluoride ions CFTX gradually decomposes, but not completely, in about 60 min, without identifying a reaction product; (ii) chloride and bromide ions determine the almost complete CFTX electro(degradation/transformation) in 10 and 5 min, respectively, with completion of the electro-transformation reaction after 60 and 30 min, respectively; (iii) instantaneous interactions between CFTX and the iodide ions occurred.

Electrocatalytic three-component annulation-halosulfonylation of 1,6-enynes toward 1-indanones using sodium halides as both halogen sources and electrolytes

A new electrochemically induced three-component annulation-halosulfonylation of 1,6-enynes has been developed for stereoselective synthesis of 33 examples of 1-indanones with generally good yields under environmentally benign conditions.