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.

Camphor and borneol are wildly distributed in the essential oils of medicinal plants from various parts of the World. Our study has been carried out to evaluate the effect of these two bicyclic monoterpenes on rat thymocytes. Camphor and borneol at concentrations of 0.5 and 5 µg/mL did not induce significant toxicity on the immune system cells, while a significant increase of thymocyte viability was detected when cells were incubated with 50 µg/mL of camphor. A significant increase of cell viability was similarly detected when thymocytes were cultivated with borneol at concentrations of 0.5 and 5 µg/mL. The role of camphor and borneol in reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) disturbances in rat thymocytes as well as their potential mechanism(s) of action were also discussed.

1H-benzimidazol-2-yl hydrazones with varying hydroxy and methoxy phenyl moieties were designed. Their effect on tubulin polymerization was evaluated in vitro on porcine tubulin. The compounds elongated the nucleation phase and slowed down the tubulin polymerization comparably to nocodazole. The possible binding modes of the hydrazones with tubulin were explored by molecular docking at the colchicine binding site. The anticancer activity was evaluated against human malignant cell lines MCF-7 and AR-230, as well as against normal fibroblast cells 3T3 and CCL-1. The compounds demonstrated a marked antineoplastic activity in low micromolar concentrations in both screened in vitro tumor models. The most active were the trimethoxy substituted derivative 1i and the positional isomers 1j and 1k, containing hydroxy and methoxy substituents: they showed IC₅₀ similar to the reference podophyllotoxin in both tumor cell lines, accompanied with high selectivity towards the malignantly transformed cells. The compounds exerted moderate to high ability to scavenge peroxyl radicals and certain derivatives—1l containing metha-hydroxy and para-methoxy group, and 1b-e with di/trihydroxy phenyl moiety, revealed HORAC values high or comparable to those of well-known phenolic antioxidants. Thus the 1H-benisimidazol-2-yl hydrazones with hydroxy/methoxy phenyl fragments were recognized as new agents exhibiting promising combined antioxidant and antineoplastic action.

Stilbenes, like resveratrol, are natural small molecules with several applications in the treatment of chronic illnesses, diabetes, and neurological and cardiovascular conditions. Considering the molecular structure of stilbenes and the biological activities of resveratrol, we investigated the synthesis and biological activity of a novel styryl quinolinium (SQ) derivative. The SQ was synthesized using the alkylation of lepidine and methyl 4-methylbenzenesulfonate and further Knoevenagel condensation with 2-hydroxy naphthaldehyde. Its structure was determined using NMR, IR, Raman, UV-Vis, and MS. The current trend of research has shifted toward the synthesis of novel SQ as resveratrol’s analog. Therefore, its anti-inflammatory and antioxidant activities were evaluated. The compound exerted very good anti-inflammatory effects in preventing albumin denaturation, which were confirmed by ex vivo immunohistochemical studies. Density functional theory (DFT) analyses were conducted on the SQ structure to gain detailed insights into its active sites, energy gap, quantum properties, and electronic behavior. The biological evaluation of the compound was completed, assessing its antioxidant potential using DPPH radical scavenging assay. In addition, molecular docking simulations were utilized to assess the SQ compound’s potential inhibitory effect on human serum albumin (HSA).

Irritable bowel syndrome (IBS) is a functional gastroenterological disorder with complex pathogenesis and multifaceted therapy approaches, aimed at alleviating clinical symptoms and improving the life quality of patients. Its treatment includes dietary changes and drugs from various pharmacological groups such as antidiarrheals, anticholinergics, serotonin receptor antagonists, targeting chloride ion channels, etc. The present article is focused on the synthesis and biological evaluation of some mebeverine precursors as potential antispasmodics. Methods: In silico analysis aimed at predicting the pharmacodynamic profile of the compounds was performed. Based on these predictions, ex vivo bioelectrical activity (BEA) and immunohistochemical effects of the compounds were established. A thorough biological evaluation of the compounds was conducted assessing their in vitro antimicrobial and cytotoxic activity. Results: All the newly synthesized compounds exerted drug-like properties, whereby 3-methyl-1-phenylbutan-2-amine 3 showed a significant change in BEA due to Ca²⁺ channel regulation, Ca²⁺ influx modulation, and a subsequent change in smooth muscle cell response. The immunohistochemical studies showed a good correlation with the obtained data on the BEA, defining amine 3 as a leader structure. No cytotoxicity to human malignant leukemic cell lines (LAMA-84, K-562) was observed for all tested compounds. Conclusion: Based on the experimental results, we outlined 3-methyl-1-phenylbutan-2-amine 3 as a potential effective choice for orally active long-term therapy of IBS.