Akademik Veri Yönetim Sistemi
JOURNAL OF MOLECULAR STRUCTURE, cilt.1307, 2024 (SCI-Expanded)
A new series of thiadiazole derivatives ( 3a -3j ) were designed and synthesized. Their structures were confirmed by spectral data and then subjected to in vitro assessment including alpha-glucosidase and tyrosinase inhibitory activities. The results of the inhibitory activity show that all the synthesized analogs effectively inhibit alpha-glucosidase and tyrosinase, with IC 50 values ranging from 0.42 +/- 0.011 to 1.83 +/- 0.076 mu M for alpha-glucosidase and 0.97 +/- 0.025 to 3.87 +/- 0.141 mu M for tyrosinase. There, compound 3e (IC 50 = 0.42 +/- 0.011 mu M) exhibited the most effective anti-alpha-glucosidase activity, with a Ki value of 0.18 +/- 0.006 mu M. Furthermore, compound 3 h (IC 50 = 0.97 +/- 0.025 mu M) showed the best tyrosinase inhibition activity with the value of Ki 0.41 +/- 0.017 mu M. Through the in silico molecular docking analysis, the ability of the synthesized analogs to inhibit alpha-glucosidase and tyrosinase was also examined. Molecular dynamics (MD) simulations and MM-GBSA calculations were performed for 3e and 3 h to support our biological findings. The favorable binding affinities and interactions displayed by both compounds with the active sites of the target enzymes illuminate their potential as competitive inhibitors. The molecular dynamics results suggest insights into the system's dynamic behavior, including the ligandreceptor complex's stability and flexibility, conformational changes, and intermolecular interactions over time. As a result of this study, it was determined that the structure of the compounds is important in drug design for diabetes and dermatological disorders.