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.

Anti-inflammatory drugs are used to relieve pain, fever, and inflammation while protecting the cardiovascular system. However, the side effects of currently available medications have limited their usage. Due to these adverse effects, there is a significant need for new drugs. The current trend of research has shifted towards the synthesis of novel anthranilic acid hybrids as anti-inflammatory agents. Phenyl- or benzyl-substituted hybrids exerted very good anti-inflammatory effects in preventing albumin denaturation. To confirm their anti-inflammatory effects, additional ex vivo tests were conducted. These immunohistochemical studies explicated the same compounds with better anti-inflammatory potential. To determine the binding affinity and interaction mode, as well as to explain the anti-inflammatory activities, the molecular docking simulation of the compounds was investigated against human serum albumin. The biological evaluation of the compounds was completed, assessing their antimicrobial activity and spasmolytic effect. Based on the experimental data, we can conclude that a collection of novel hybrids was successfully synthesized, and they can be considered anti-inflammatory drug candidates—alternatives to current therapeutics.

Chronic, multifactorial illnesses of the gastrointestinal tract include inflammatory bowel diseases. One of the greatest methods for regulated medicine administration in a particular region of inflammation is the nanoparticle system. Silver nanoparticles (Ag NPs) have been utilized as drug delivery systems in the pharmaceutical industry. The goal of the current study is to synthesize drug-loaded Ag NPs using a previously described 3-methyl-1-phenylbutan-2-amine, as a mebeverine precursor (MP). Methods: A green, galactose-assisted method for the rapid synthesis and stabilization of Ag NPs as a drug-delivery system is presented. Galactose was used as a reducing and capping agent forming a thin layer encasing the nanoparticles. Results: The structure, size distribution, zeta potential, surface charge, and the role of the capping agent of drug-loaded Ag NPs were discussed. The drug release of the MP-loaded Ag NPs was also investigated. The Ag NPs indicated a very good drug release between 80 and 85%. Based on the preliminary results, Ag NPs might be a promising medication delivery system for MP and a useful treatment option for inflammatory bowel disease. Therefore, future research into the potential medical applications of the produced Ag NPs is necessary.

Propolis is a complex honey bee product known for its antioxidant potential and antimicrobial activity, widely used as a food biopreservative and food additive. The object of the current research was to investigate the effects of carboxymethyl cellulose (CMC) edible coatings applied alone and in combination with a propolis extract on the quality parameters and storage life of fresh blueberries during refrigerated storage for 20 days. For this purpose, three experimental groups were prepared: blueberries without coating (control group), blueberries with 1% CMC coatings and blueberries with 1% CMC coatings + 1% propolis extract (CMC+P). During the storage, the physicochemical and microbiological parameters of the experimental groups were evaluated. The use of CMC and CMC+P coatings reduced the weight loss by 1.13% and 1.67% in comparison with the control group on the 20-th day of storage. A significant decrease in decay percentage was found, which was in the great extent in the CMC+P coated fruit compared to the CMC coatings and the control fruit. The CMC and CMC+P edible coatings did not affect the TSS levels, the decreasing TA and increasing pH values. The application of CMC and CMC+P coatings did not cause a protective effect on the lowering values of total phenolic and anthocyanin contents in both treatments, but exhibited a positive influence on the antioxidant activity in the coated blueberries. During the entire storage period, propolis containing edible coatings (CMC+P) reduced the bacterial, yeasts and fungal counts, visibly expressed by a reduction in decay incidence in comparison with the uncoated and CMC-treated fruit. Therefore, the application of propolis in the composition of edible coatings can be considered as an effective approach for improving the postharvest quality and prolonging the storage life of fresh blueberries.

Propolis (bee glue) is a complex biological product known for its antimicrobial activity and antioxidant potential, and widely used as food additive and biopreservative. The aim of the present research was to examine the effects of propolis on the improvement of the storage life of ripened kashkaval cheese. For this purpose, three types of 1% carboxymethyl cellulose edible films containing three different ethanolic propolis extracts in concentration of 1% were prepared. Double-layer edible films were applied on the kashkaval cheese surface, and the samples were designated as T1, T2, and T3. An untreated sample was kept as a control. The four experimental groups (T1, T2, T3, and control) were then stored under refrigeration conditions at 4°C and 75% relative humidity (RH) for 56 days. During the storage period, the cheese was observed for visible changes, and samples for physicochemical and microbiological analyses were taken. The results from physicochemical analysis demonstrated that values of titratable acidity decreased in all experiment groups during the storage period. The results from microbiological analysis revealed that three types of edible films T1, T2, and T3 did not affect the decreasing number of lactic acid bacteria, a normal process for the period after the cheese ripening. The application of T1, T2, and T3 edible films did not affect the increasing number of yeasts in kashkaval cheese through the storage period. However, T1 and T2 edible films effectively inhibited the fungal growth on cheese surface, and no signs of spoilage were observed until the end of the storage for 56 days. In contrast, T3 treatment delayed but did not inhibit the fungal growth, and the first signs of fungal decay appeared between the 35th and 42nd day of the storage, compared to the control (28th day). Thus, the application of propolis can be considered an effective means for the prevention of fungal spoilage of kashkaval cheese.