5-Aryl-furan derivatives bearing a phenylalanine- or isoleucine-derived rhodanine moiety as potential PTP1B inhibitors

Tianwei Niu; Peipei Wang; Cheng Li; Tong Dou; Huri Piao; Jia Li; Liangpeng Sun

doi:10.1016/j.bioorg.2020.104483

5-Aryl-furan derivatives bearing a phenylalanine- or isoleucine-derived rhodanine moiety as potential PTP1B inhibitors

Bioorg Chem. 2021 Jan:106:104483. doi: 10.1016/j.bioorg.2020.104483. Epub 2020 Nov 19.

Authors

Tianwei Niu¹, Peipei Wang², Cheng Li³, Tong Dou⁴, Huri Piao⁴, Jia Li⁵, Liangpeng Sun⁶

Affiliations

¹ College of Medicine, Yanbian University, Yanji 133000, China; China-Japan Union Hospital of Jilin University, Changchun 130033, China.
² National Center for Drug Screening, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Science, Chinese Academy of Sciences, Shanghai 201203, China.
³ College of Medicine, Yanbian University, Yanji 133000, China; Department of Pharmacy, Yanbian University Hospital, Yanji 133000, China.
⁴ College of Pharmacy, Yanbian University, Yanji 133000, China.
⁵ National Center for Drug Screening, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Science, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: [email protected].
⁶ College of Medicine, Yanbian University, Yanji 133000, China; College of Pharmacy, Yanbian University, Yanji 133000, China. Electronic address: [email protected].

PMID: 33268007
DOI: 10.1016/j.bioorg.2020.104483

Abstract

Two series of 5-aryl-furan derivatives bearing a phenylalanine- or isoleucine-derived rhodanine moiety were identified as competitive protein tyrosine phosphatase 1B (PTP1B) inhibitors. Among the compounds studied, 5g was found to have the best PTP1B inhibitory potency (IC₅₀ = 2.66 ± 0.16 µM) and the best cell division cycle 25 homolog B (CDC25B) inhibitory potency (IC₅₀ = 0.25 ± 0.02 µM). Enzymatic data together with molecular modeling results demonstrated that the introduction of a sec-butyl group at the 2-position of the carboxyl group remarkably improved the PTP1B inhibitory activity.

Keywords: Furan; Isoleucine; PTP1B inhibitor; Phenylalanine; Rhodanine.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Dose-Response Relationship, Drug
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Furans / chemical synthesis
Furans / chemistry
Furans / pharmacology*
Humans
Isoleucine / chemistry
Isoleucine / pharmacology*
Molecular Structure
Phenylalanine / chemistry
Phenylalanine / pharmacology*
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism
Rhodanine / chemistry
Rhodanine / pharmacology*
Structure-Activity Relationship

Substances

Enzyme Inhibitors
Furans
Isoleucine
Phenylalanine
Rhodanine
PTPN1 protein, human
Protein Tyrosine Phosphatase, Non-Receptor Type 1