Synthesis and Evaluation of Dibenzothiophene Analogues as Pin1 Inhibitors for Cervical Cancer Therapy
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.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2019 |
---|---|
Erschienen: |
2019 |
Enthalten in: |
Zur Gesamtaufnahme - volume:4 |
---|---|
Enthalten in: |
ACS omega - 4(2019), 5 vom: 31. Mai, Seite 9228-9234 |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Wu, Ke-Jia [VerfasserIn] |
---|
Links: |
---|
Themen: |
---|
Anmerkungen: |
Date Revised 04.11.2023 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
---|
doi: |
10.1021/acsomega.9b00281 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM300695454 |
---|
LEADER | 01000naa a22002652 4500 | ||
---|---|---|---|
001 | NLM300695454 | ||
003 | DE-627 | ||
005 | 20231225103106.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231225s2019 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1021/acsomega.9b00281 |2 doi | |
028 | 5 | 2 | |a pubmed24n1002.xml |
035 | |a (DE-627)NLM300695454 | ||
035 | |a (NLM)31460012 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Wu, Ke-Jia |e verfasserin |4 aut | |
245 | 1 | 0 | |a Synthesis and Evaluation of Dibenzothiophene Analogues as Pin1 Inhibitors for Cervical Cancer Therapy |
264 | 1 | |c 2019 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Revised 04.11.2023 | ||
500 | |a published: Electronic-eCollection | ||
500 | |a Citation Status PubMed-not-MEDLINE | ||
520 | |a 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 | ||
650 | 4 | |a Journal Article | |
700 | 1 | |a Liu, Xie |e verfasserin |4 aut | |
700 | 1 | |a Wong, Suk-Yu |e verfasserin |4 aut | |
700 | 1 | |a Zhou, Yuyang |e verfasserin |4 aut | |
700 | 1 | |a Ma, Dik-Lung |e verfasserin |4 aut | |
700 | 1 | |a Leung, Chung-Hang |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t ACS omega |d 2016 |g 4(2019), 5 vom: 31. Mai, Seite 9228-9234 |w (DE-627)NLM264243048 |x 2470-1343 |7 nnns |
773 | 1 | 8 | |g volume:4 |g year:2019 |g number:5 |g day:31 |g month:05 |g pages:9228-9234 |
856 | 4 | 0 | |u http://dx.doi.org/10.1021/acsomega.9b00281 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 4 |j 2019 |e 5 |b 31 |c 05 |h 9228-9234 |