Many non-steroidal anti-inflammatory drugs (NSAIDs) concurrently inhibit both COX-1 and COX-2, with a preference for specifically targeting COX-2 due to its significant involvement in various pathologies. In addition to COX enzymes, several other targets, including Aldose reductase, Aldo-ketoreductase family 1-member C2, and Phospholipase A2, have been identified as contributors to inflammation and a myriad of other diseases.

Diabetes mellitus remains a global health challenge, necessitating the development of novel therapeutic agents. In this study, a series of thiohydantoin derivatives (FP1–FP7) were synthesized and evaluated for their in silico, in vitro, and in vivo antidiabetic potential. Molecular docking studies revealed strong binding affinities of derivatives towards α-glucosidase (PDB: 3wy1) and α-amylase (PDB: 3dhp), with FP4 exhibiting the most favorable interactions (− 7.8 kcal/mol with α-amylase and − 7.0 kcal/mol with α-glucosidase), involving hydrogen bonding and π-π stacking. During in vitro enzyme inhibition assay, FP4 demonstrated potent inhibitory activity against α-glucosidase and α-amylase, with IC₅₀ values of 129.40 and 128.90 µg/mL, respectively. The DPPH scavenging assay also indicated that FP4 had relatively strong antioxidant activity, with an IC₅₀ value of 39.7 µg/mL. In vivo antidiabetic efficacy was evaluated in STZ-induced diabetic rats over a period of 6-week. FP4 treated diabetic rats exhibited significantly reduced fasting blood glucose by 28.9% than in diabetic controls. In addition, HbA1C levels and diabetes-associated weight loss were significantly curtailed in these animals than untreated diabetic group. Further FP4 treated animals exhibited significantly decreased LDL and triglyceride levels and elevated HDL levels, suggesting a broader metabolic benefit. Taken together, our results suggest that thiohydantoin derivatives, particularly FP4, exhibited interesting antidiabetic and antihyperlipidemic activities warranting further pharmacokinetic and mechanistic investigations also potential for clinical translation and long term safety assessment.

Introduction: Right now, we are facing a global pandemic caused by the coronavirus SARS-CoV-2 that causes the highly contagious human disease COVID-19. The number of COVID-19 cases is increasing at an alarming rate, more and more people suffer from it, and the death toll is on the rise since December 2019, when COVID-19 has presumably appeared. We need an urgent solution for the prevention, treatment, and recovery of the involved patients. Methods: Modulated electro-hyperthermia (mEHT) is known as an immuno-supportive therapy in oncology. Our proposal is to apply this method to prevent the progression of the disease after its identification, to provide treatment when necessary, and deliver rehabilitation to diminish the fibrotic—often fatal—consequences of the infection. Hypothesis: The effects of mEHT, which are proven for oncological applications, could be utilized for the inactivation of the virus or for treating the fibrotic consequences. The hypothesized mEHT effects, which could have a role in the antiviral treatment, it could be applied for viral-specific immune-activation and for anti-fibrotic treatments.

Chronic inflammatory disorders are often accompanied by persistent pain, yet current therapies remain limited by modest efficacy and adverse effects. To address this challenge, a series of eleven chalcone-based derivatives was synthesized via Claisen–Schmidt condensation and structurally characterized by FTIR, ¹H-NMR, ¹³C-NMR, and EIMS analyses. Cytotoxicity assessment on 3T3 fibroblasts using the MTT assay revealed no toxicity compared to doxorubicin, while brine shrimp lethality and hemolytic assays further confirmed their safety profile. In vitro COX-1/2 assays demonstrated preferential inhibition of COX-2, with AS1-6 showing a superior selectivity index relative to nimesulide. In vivo screening corroborated these results: AS1-2, AS1-6, and AS1-8 produced significant anti-inflammatory effects in carrageenan-induced paw edema, while AS1-2, AS1-6, and AS1-10 suppressed nociceptive behaviours in the formalin test, indicating both peripheral and central antinociceptive activity. Ex vivo ELISA further verified down-regulation of COX-2-associated inflammatory mediators compared to negative group. Molecular docking revealed strong and selective interactions of AS1-2 and AS1-6 within the COX-2 active site, while sparing COX-1. Molecular dynamics simulations confirmed the stability of AS1-6 in the active pocket throughout a 100 ns trajectory, consistent with the pharmacological outcomes. Collectively, the concordance of in vitro COX-1/2 inhibition, in vivo efficacy, and in silico analyses underscores the potential of these chalcone analogues as selective COX-2 inhibitors. These findings highlight the value of structure-guided design in developing dual-function chalcones with anti-inflammatory and antinociceptive activity, warranting further optimization and preclinical evaluation.

Acetylcholinesterase (AChE) plays a pivotal role in Alzheimer's disease by accelerating acetylcholine breakdown, leading to cognitive decline.