Abstract:
:α-Glucosidase is known to catalyze the digestion of carbohydrates and release free glucose into the digestive tract. Protein tyrosine phosphatase 1B (PTP1B) is engaged in the dephosphorylation of the insulin receptor and regulation of insulin sensitivity. Therefore, dual antagonists by targeting both α-glucosidase and PTP1B may be potential candidates for type 2 diabetes therapy. In this work, three series of novel N-aryl-ω-(benzoazol-2-yl)-sulfanylalkanamides were synthesized and assayed for their α-glucosidase and PTP1B inhibitory activities, respectively. Compound 3l, exhibiting the most effective α-glucosidase inhibitory activity (IC50 = 10.96 μm (3l), IC50 = 51.32 μm (Acarbose), IC50 = 18.22 μm (Ursolic acid)) and potent PTP1B inhibitory activity (IC50 = 13.46 μm (3l), IC50 = 14.50 μm (Ursolic acid)), was identified as a novel dual inhibitor of α-glucosidase and PTP1B. Furthermore, 3l is a highly selective PTP1B inhibitor because no inhibition was showed by 3l at 100 μm against PTP-MEG2, TCPTP, SHP2, or SHP1. Subsequent kinetic analysis revealed 3l inhibited α-glucosidase in a reversible and mixed manner. Molecular docking study indicated that hydrogen bonds, van der Waals, charge interactions and Pi-cation interactions all contributed to affinity between 3l and α-glucosidase/PTP1B.
journal_name
Chem Biol Drug Desjournal_title
Chemical biology & drug designauthors
Wang MY,Cheng XC,Chen XB,Li Y,Zang LL,Duan YQ,Chen MZ,Yu P,Sun H,Wang RLdoi
10.1111/cbdd.13331subject
Has Abstractpub_date
2018-09-01 00:00:00pages
1647-1656issue
3eissn
1747-0277issn
1747-0285journal_volume
92pub_type
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