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Synthesis and biological evaluation of geniposide derivatives as potent and selective PTPlB inhibitors.

Abstract：

:Herein a series of Geniposide derivatives were designed, synthesized and evaluated as protein tyrosine phosphatase 1B (PTPlB) inhibitors. Most of these compounds exhibited potent in vitro PTP1B inhibitory activities, the representative 7a and 17f were found to be the most potent inhibitors against the enzyme with IC50 values of 0.35 and 0.41 μM, respectively. More importantly, they showcased 4 to10-fold selectivity over SHP2 and 3-fold over TCPTP. Further biological activity studies revealed that compounds 7a, 17b and 17f could effectively enhance insulin-stimulated glucose uptake with no significant cytotoxicity. Subsequent molecular docking and structural activity relationship analyses demonstrated that the glucose scaffold, benzylated glycosyl groups, and arylethenesulfonic acid ester significantly impact on the activity and selectivity.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Lei S,Zhang D,Qi Y,Chowdhury SR,Sun R,Wang J,Du Y,Fu L,Jiang F

doi

10.1016/j.ejmech.2020.112508

subject

Has Abstract

pub_date

2020-11-01 00:00:00

pages

112508

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(20)30480-3

journal_volume

205

pub_type

杂志文章

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