Novel Coumarin Derivatives Containing a Triazole Moiety: A Study on Synthesis, Cytotoxicity, Membrane Dysfunction, Apoptosis, Cell Cycle, and Antiangiogenic Effects

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dc.authoridGUNER, ADEM/0000-0003-3295-3538
dc.contributor.authorGuner, Adem
dc.contributor.authorBektas, Hakan
dc.contributor.authorMentese, Emre
dc.date.accessioned2025-03-23T19:27:12Z
dc.date.available2025-03-23T19:27:12Z
dc.date.issued2022
dc.departmentSinop Üniversitesi
dc.description.abstractBackground: Coumarin is a functional compound with a pronounced wide range of biological activities and has recently been shown to have anticancer effects on various human cancer cells. Cisplatin is widely used in treating many cancers, but its effectiveness is limited due to acquired resistance and dose-related side effects. Objective: This study aimed to reveal the chemosensitizing ability of novel synthesized coumarin-triazole hybrid compounds (3a-f) compared to the cisplatin in A549, MCF-7, and HeLa cancer cells. Methods: Cytotoxicity was determined by MTT assay. Lactate dehydrogenase (LDH), antioxidant/oxidant status, and DNA fragmentation were determined spectrophotometrically using commercial kits. Muse (TM) Cell Analyzer was used to assess cell cycle progression. Pro/anti-apoptotic gene expressions were determined by Real-Time qPCR. The antiangiogenic activity was determined by VEGF expression and Hen's chorioallantoic membrane model. Results: Compounds 3c, -d, -e, and -f potentiated the cisplatin-induced cytotoxicity by increasing LDH release and DNA fragmentation, inducing G2/M cell cycle arrest, overproducing oxidative stress, and decreasing cellular antioxidant levels. These compounds combined with cisplatin caused upregulation in the pro-apoptotic Bax, Bid, caspase-3, caspase-8, caspase-9, Fas, and p53 gene expressions while downregulating anti-apoptotic DFFA, NFkB1, and Bcl2 gene expressions. These combinations caused vascular loss and a reduction in VEGF expression. Conclusion: These results suggest that a combinational regimen of coumarin compounds with cisplatin could enhance the effect of cisplatin in A549 cells. Besides, these compounds exhibit relatively low toxicity in normal cells, thus decreasing the dose requirement of cisplatin in cancer treatments.
dc.identifier.doi10.2174/1871520622666220106104324
dc.identifier.endpage2438
dc.identifier.issn1871-5206
dc.identifier.issn1875-5992
dc.identifier.issue13
dc.identifier.pmid34994335
dc.identifier.scopus2-s2.0-85132156442
dc.identifier.scopusqualityQ2
dc.identifier.startpage2429
dc.identifier.urihttps://doi.org/10.2174/1871520622666220106104324
dc.identifier.urihttps://hdl.handle.net/11486/4865
dc.identifier.volume22
dc.identifier.wosWOS:000832560300009
dc.identifier.wosqualityQ3
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherBentham Science Publ Ltd
dc.relation.ispartofAnti-Cancer Agents in Medicinal Chemistry
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_WOS_20250323
dc.subjectCisplatin
dc.subjectcoumarin
dc.subjectcytotoxicity
dc.subjectlung cancer
dc.subjectresistance
dc.subjectROS
dc.titleNovel Coumarin Derivatives Containing a Triazole Moiety: A Study on Synthesis, Cytotoxicity, Membrane Dysfunction, Apoptosis, Cell Cycle, and Antiangiogenic Effects
dc.typeArticle

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