Synthesis of Novel Triazole-Urea Hybrids and Their Antiproliferative Activity Against Pancreatic Cancer Through Suppression of Eef2k and Induction of Apoptosis

dc.authorid ARMAGAN, GULIZ/0000-0001-6466-2263
dc.authorid Cevik, Ozge/0000-0002-9325-3757
dc.authorid Erdogan, Mumin/0000-0003-0048-444X
dc.authorscopusid 57205129849
dc.authorscopusid 59013638700
dc.authorscopusid 59013375200
dc.authorscopusid 25935885100
dc.authorscopusid 57189713929
dc.authorscopusid 57208031609
dc.authorscopusid 24400636500
dc.authorwosid Armagan, Guliz/ABI-5508-2020
dc.authorwosid Ozdemir, Burcu/AAK-6536-2021
dc.authorwosid Erdogan, Omer/AAW-5497-2021
dc.authorwosid Erdogan, Mumin/AAR-3140-2021
dc.authorwosid Cevik, Ozge/F-1326-2014
dc.contributor.author Küçükgüzel, İlkay
dc.contributor.author Ozdemir, Burcu
dc.contributor.author Cece, Onur
dc.contributor.author Armagan, Guliz
dc.contributor.author Erdogan, Mumin Alper
dc.contributor.author Erdogan, Omer
dc.contributor.author Kucukguzel, Ilkay
dc.contributor.other Eczacılık Meslek Bilimleri Bölümü
dc.date.accessioned 2025-01-11T13:02:17Z
dc.date.available 2025-01-11T13:02:17Z
dc.date.issued 2024
dc.department Fenerbahçe University en_US
dc.department-temp [Tuere, Asli; Ozdemir, Burcu; Cece, Onur] Marmara Univ, Fac Pharm, Dept Pharmaceut Chem, Istanbul, Turkiye; [Armagan, Guliz] Ege Univ, Fac Pharm, Dept Biochem, Izmir, Turkiye; [Erdogan, Mumin Alper] Izmir Katip Celebi Univ, Sch Med, Dept Physiol, Izmir, Turkiye; [Erdogan, Omer] Gaziantep Islam Sci & Technol Univ, Sch Med, Dept Biochem, Gaziantep, Turkiye; [Cevik, Ozge] Adnan Menderes Univ, Sch Med, Dept Biochem, Aydin, Turkiye; [Kucukguzel, Ilkay] Fenerbahce Univ, Fac Pharm, Dept Pharmaceut Chem, Istanbul, Turkiye en_US
dc.description ARMAGAN, GULIZ/0000-0001-6466-2263; Cevik, Ozge/0000-0002-9325-3757; Erdogan, Mumin/0000-0003-0048-444X en_US
dc.description.abstract Pancreatic cancer is one of the deadliest cancers with its highly aggressive and metastatic character and there is a huge unmet need for new drugs treating pancreatic cancer. In the present study, a series of 1,2,4-triazole-urea conjugates have been designed and synthesized as novel candidates of antiproliferative agents against pancreatic cancer cells. Among them, compounds 33, 34, 35 and 38 possesing IC50 values between 0.231 and 0.488 mu M against PANC-1 cells demonstrated the highest anti-proliferative activity. These compounds presenting the highest antiproliferative activity were evaluated for further biological studies. The same four compounds inhibited colony formation in pancreatic cancer cells dose dependently. Western blot study on the selected compounds showed that compounds 33 and 38 significantly reduced eEF2K protein levels in cancer cells. These compounds displayed an effective eEF2K activity suppression by down-regulated levels of unphosphorylated eEF2 in PANC-1 cells. Compounds 33, 34, 35 and 38 were also demonstrated to induce apoptosis and activate caspase 3/7. In silico studies were performed to predict the druggability and ADMET/ properties of the active molecules. In summary, 1,2,4-triazole-urea conjugates developed in this study represent a novel and promising lead structure with anticancer activity against pancreatic cancer achieved through eEF2K activity suppression. Compounds being referred to are the first "triazole-urea hybrid" molecules found to be effective against pancreatic cancer. en_US
dc.description.sponsorship TUBITAK [1919B011901945] en_US
dc.description.sponsorship The authors express their appreciation to TUBITAK (2209-A project no: 1919B011901945) for providing partial financial support. en_US
dc.description.woscitationindex Science Citation Index Expanded
dc.identifier.citation 0
dc.identifier.doi 10.1016/j.molstruc.2024.138428
dc.identifier.issn 0022-2860
dc.identifier.issn 1872-8014
dc.identifier.scopus 2-s2.0-85192074373
dc.identifier.scopusquality Q1
dc.identifier.uri https://doi.org/10.1016/j.molstruc.2024.138428
dc.identifier.uri https://hdl.handle.net/20.500.14627/220
dc.identifier.volume 1311 en_US
dc.identifier.wos WOS:001238036000001
dc.identifier.wosquality Q2
dc.language.iso en en_US
dc.publisher Elsevier en_US
dc.relation.publicationcategory Makale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı en_US
dc.rights info:eu-repo/semantics/closedAccess en_US
dc.scopus.citedbyCount 0
dc.subject 4-Triazoles en_US
dc.subject Urea Derivatives en_US
dc.subject Pancreatic Cancer en_US
dc.subject Eef2K en_US
dc.subject Apoptosis en_US
dc.subject In Silico en_US
dc.title Synthesis of Novel Triazole-Urea Hybrids and Their Antiproliferative Activity Against Pancreatic Cancer Through Suppression of Eef2k and Induction of Apoptosis en_US
dc.type Article en_US
dc.wos.citedbyCount 0
dspace.entity.type Publication
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