Turkish Journal of Chemistry
The 4-(dimethylaminoalkyl)piperazine inhibitors of α-glucosidase: allosteric enzyme inhibition and identification of interacting chemical groups
In continuation of our interest in identifying new α-glucosidase inhibitors with potential to become antidiabetic drugs, this work focuses on the study of 4-(dimethylaminoalkyl)piperazine-1-carbodithioate derivatives as α-glucosidase inhibitors. The eight heterocyclic piperazine-dithiocarbamate complexes studied in this work contain a variety of substitutions on their benzene ring exhibiting potent, noncompetitive inhibition of α-glucosidase. Dithiocarbamate and piperazine moieties are important pharmacophores with promising therapeutic prospects featuring facilitated drug delivery due to their lipophilic nature in addition to their α-glucosidase inhibitory activity. Enzyme kinetics, molecular dynamics simulations, and docking studies revealed that the target compounds bind to a new allosteric site that is located near the active site of α-glucosidase. Majority of molecular interactions of the compounds with the enzyme are mediated by hydrophobic contacts in addition to a number of important polar interactions. The current work identifies a number of chemical groups in the compounds that are responsible for potent inhibition of α-glucosidase. Moreover, it also provides new insights into understanding α-glucosidase inhibition by dithiocarbamate and piperazine-containing compounds that can be promising for development of new antidiabetic drugs.
Alpha-glucosidase inhibitor, dithiocarbamate, piperazine, noncompetitive, allosteric
GHANI, USMAN; ASHRAF, SAJDA; HAQ, ZAHEER UL; KAPLANCIKLI, ZAFER ASIM; DEMİRCİ, FATİH; ÖZKAY, YUSUF; and AFZAL, SIBTAIN
"The 4-(dimethylaminoalkyl)piperazine inhibitors of α-glucosidase: allosteric enzyme inhibition and identification of interacting chemical groups,"
Turkish Journal of Chemistry: Vol. 46:
5, Article 11.
Available at: https://journals.tubitak.gov.tr/chem/vol46/iss5/11