Mina Todorova

The present article focuses on the synthesis and biological evaluation of a novel anthranilic acid hybrid and its diamides as antispasmodics. Methods: Due to the predicted in silico methods spasmolytic activity, we synthesized a hybrid molecule of anthranilic acid and 2-(3-chlorophenyl)ethylamine. The obtained hybrid was then applied in acylation with different acyl chlorides. Using in silico analysis, pharmacodynamic profiles of the compounds were predicted. A thorough biological evaluation of the compounds was conducted assessing their in vitro antimicrobial, cytotoxic, anti-inflammatory activity, and ex vivo spasmolytic activity. Density functional theory (DFT) calculation, including geometry optimization, molecular electrostatic potential (MEP) surface, and HOMO-LUMO analysis for the synthesized compounds was conducted using the B3LYP/6–311G(d,p) method to explore the electronic behavior, reactive regions, and stability and chemical reactivity of the compounds. Furthermore, molecular docking simulation along with viscosity measurement indicated that the newly synthesized compounds interact with DNA via groove binding mode. The obtained results from all the experiments demonstrate that the hybrid molecule and its diamides inherit spasmolytic, antimicrobial, and anti-inflammatory capabilities, making them excellent candidates for future medications.

Anticoagulants prevent the blood from developing the coagulation process, which is the primary cause of death in thromboembolic illnesses. Phenindione (PID) is a well-known anticoagulant that is rarely employed because it totally prevents coagulation, which can be a life-threatening complication. The goal of the current study is to synthesize drug-loaded Ag NPs to slow down the coagulation process. Methods: A rapid synthesis and stabilization of silver nanoparticles as drug-delivery systems for phenindione (PID) were applied for the first time. Results: Several methods are used to determine the size of the resulting Ag NPs. Additionally, the drug-release capabilities of Ag NPs were established. Density functional theory (DFT) calculations were performed for the first time to indicate the nature of the interaction between PID and nanostructures. DFT findings supported that galactose-loaded nanostructure could be a proper delivery system for phenindione. The drug-loaded Ag NPs were characterized in vitro for their antimicrobial, cytotoxic, and anticoagulant activities, and ex vivo for spasmolytic activity. The obtained data confirmed the drug-release experiments. Drug-loaded Ag NPs showed that prothrombin time (PT, sec) and activated partial thromboplastin time (APTT, sec) are approximately 1.5 times longer than the normal values, while PID itself stopped coagulation at all. This can make the PID-loaded Ag NPs better therapeutic anticoagulants. PID was compared to PID-loaded Ag NPs in antimicrobial, spasmolytic activity, and cytotoxicity. All the experiments confirmed the drug-release results.

Propolis (bee glue), a valuable biological mixture produced by European honey bees ( Apis mellifera L.), is widely used as a remedy in traditional and alternative medicine, as an effective food biopreservative and as a nutritional value enhancer. The present study aimed to investigate eighty propolis samples collected from all twenty-eight districts of Bulgaria in the period of 2020–2022 in order to determine their physicochemical properties as well as their antioxidant and antimicrobial potential. The raw propolis samples exhibited brown or green colour depending on the climatic zone from which they are collected and pH values from 4.82 to 5.87, while the moisture content ranged between 0.98% and 2.97%. The total phenolics content (TPC) and total flavonoids content (TFC) varied from 63.14 mg GAE/g to 737.27 mg GAE/g, and from 29.22 mg QE/g to 234.17 mg QE/g, respectively. The propolis samples demonstrated significant antioxidant potential determined by DPPH and FRAP methods, from 18.56 mM TE/g to 1598.66 mM TE/g and from 82.28 mM TE/g to 1208.81 mM TE/g, respectively, whose values showed a positive correlation ( r 2 ) with the TPC and TFC. The results from the antimicrobial screening revealed that the methanolic propolis extracts in concentration of 20 mg/ml exhibited the highest inhibitory effect on the Gram-positive bacteria such as Micrococcus luteus 2YC-YT, Bacillus subtilis ATCC 6633, Staphylococcus aureus ATCC 25923, Listeria monocytogenes NBIMCC 8632 and Listeria innocua ATCC 33090.