No abstract

In the present study, new structural variants of 4-hydroxyquinolinone-hydrazones were designed and synthesized. The structure elucidation of the synthetic derivatives 6a–o was carried out using different spectroscopic techniques including FTIR, 1H-NMR, 13C-NMR, and elemental analysis, and their α-glucosidase inhibitory activity was also determined. The synthetic molecules 6a–o exhibited good α-glucosidase inhibition with IC50 values ranging between 93.5 ± 0.6 to 575.6 ± 0.4 µM as compared to the standard acarbose (IC50 = 752.0 ± 2.0 µM). Structure–activity relationships of this series were established which is mainly based on the position and nature of the substituent on the benzylidene ring. A kinetic study of the active compounds 6l and 6m as the most potent derivatives were also carried out to confirm the mode of inhibition. The binding interactions of the most active compounds within the active site of the enzyme were determined by molecular docking and molecular dynamic simulations.

Background Tumor Necrosis Factor-alpha (TNF-alpha) inhibitors, such as adalimumab (ADA) and infliximab (IFX), are among the most effective biological drugs for inducing and maintaining remission in patients with moderate to severe inflammatory bowel disease (IBD). Previous studies have shown that the effectiveness of IFX is increased with the concomitant use of immunosuppressive drugs. However, little is known about the benefits of adding other immunosuppressive agents to ADA. This study compared the efficacy of monotherapy with biosimilar adalimumab (ADA) and combination therapy with ADA + azathioprine (AZA) in IBD patients. Methods In this retrospective cohort study, we evaluated the medical records of anti-TNF-naïve IBD patients referred to Imam Khomeini Hospital in Tehran during, 2019–2020 and were prescribed with biosimilar ADA (CinnoRA®). We compared the effectiveness of treatment, serum levels of ADA, anti-adalimumab antibodies (AAAs), and laboratory data between the two monotherapy and combination therapy groups. Results A total of, 65 patients were enrolled in the study. Fifty-six (86.2%) patients had ulcerative colitis (UC), and the remaining had Crohn’s disease (CD). Fifty patients (76.9%) received combination therapy, and, 15 (23.1%) patients were under monotherapy. The rate of clinical remission in the combination therapy group (50%) did not differ significantly from the monotherapy group (40%) (P=0.56). The drug levels were in the therapeutic range (≥7.5 µg/mL) in, 57.5% of patients in the combination therapy group and, 76.9% of those in the monotherapy group (P=0.21). The antibody test result was positive in, 40% of patients taking AZA + ADA and, 10% of patients in the ADA group (P=0.21). Conclusion There was no significant difference in the ADA and AAA concentrations between patients receiving ADA monotherapy and combination therapy. Moreover, there was no association between ADA concentrations and the rate of remission in IBD patients. Hence, AZA does not affect the efficacy and pharmacokinetics of ADA in patients with IBD.