Synthesis, in vitro, and in silico studies of 7-fluorochromone based thiosemicarbazones as α-glucosidase inhibitors
Faiqa Noreen, Naeem Ullah, Suraj N. Mali, Ajmal Khan, Javid Hussain, Abdulrahman Alshammari, Norah A. Albekairi, Rahul D. Jawarkar, Susmita Yadav, Ahmed Al-Harrasi, Zahid Shafiq
Abstract
Increased blood sugar is a typical manifestation of Type-2 Diabetes Mellitus (T2DM), a metabolic disorder that can be effectively managed with the help of α-glucosidase inhibitors. A range of new chromone based thiosemicarbazone derivatives (3a-t) was synthesized and assessed due to their ability to suppress α-glucosidase in this research. Having IC 50 values spanning from 6.40 ± 0.15 to 62.81 ± 0.79 μM, the compounds demonstrated strong inhibitory actions. The compound 3 k showed the most inhibitory effect among all of them, by an IC 50 measurement of 6.40 ± 0.15 µM. It was concluded through a structure–activity relationship (SAR) assessment that various substituents on thiosemicarbazone moieties had a significant impact on the differences in α-glucosidase inhibition. Molecular docking experiments provide light on important interactions, including π-π interactions and hydrogen bridges, between compounds and role of the carbothioamide and chromenyl groups in ligand attachment to the critical residues of α-glucosidase. The binding interactions, alignment, stability, and structural arrangement of the prepared molecules in the catalytic pocket of α-glucosidase were explored using in silico strategies such as docking studies, pharmacokinetic analysis, and molecular dynamics simulations. This investigation directed to find compounds with favorable profiles for future progress as potential therapeutic agents for type 2 diabetes. Importantly, when benchmarking against acarbose, the lead candidate showed substantially greater efficacy.