Synthesis and Evaluation of Dibenzothiophene Analogues as Pin1 Inhibitors for Cervical Cancer Therapy

Ke Jia Wu, Xie Liu, Suk Yu Wong, Yuyang Zhou*, Edmond Dik Lung MA, Chung Hang Leung

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

The peptidyl-prolyl isomerase Pin1 is correlated with the progression of cervical cancer via regulating numerous oncogenic and tumor suppressor pathways. p65 is a crucial regulator of tumorigenesis that is regulated by Pin1, and p65 signaling suppression can enhance the antitumor efficacy of doxorubicin (DOX). Here, we utilized a structural mimicry approach to synthesize a series of dibenzothiophene analogues and evaluated their ability to inhibit Pin1 activity. Compound 1a was identified as a potent Pin1 inhibitor that inhibited p65 signaling in vitro and in cervical cancer cells. Moreover, compound 1a enhanced the cytotoxicity of DOX in cervical cancer cells via reducing p65 nuclear accumulation and enhancing DOX uptake. These compounds are promising scaffolds for developing more potent Pin1 inhibitors against cervical cancer, either alone or in combination with anticancer drugs such as DOX.

Original languageEnglish
Pages (from-to)9228-9234
Number of pages7
JournalACS Omega
Volume4
Issue number5
DOIs
Publication statusPublished - 24 May 2019

Scopus Subject Areas

  • Chemistry(all)
  • Chemical Engineering(all)

Fingerprint

Dive into the research topics of 'Synthesis and Evaluation of Dibenzothiophene Analogues as Pin1 Inhibitors for Cervical Cancer Therapy'. Together they form a unique fingerprint.

Cite this