Synthesis and Anti-Hcv Activity of Novel 5-Arylmethylene Derivatives Via Suppression of Ns5b Polymerase and Cox-2

dc.authorscopusid57190582389
dc.authorscopusid59467907500
dc.authorscopusid39161700400
dc.authorscopusid6603485785
dc.authorwosidLee, Jin-Ching/C-9676-2009
dc.contributor.authorKüçükgüzel, İlkay
dc.contributor.authorLee, Jin-Ching
dc.contributor.authorOzakpinar, Ozlem Bingol
dc.contributor.authorKucukguzel, Ilkay
dc.contributor.otherEczacılık Meslek Bilimleri Bölümü
dc.date.accessioned2025-01-11T13:02:16Z
dc.date.available2025-01-11T13:02:16Z
dc.date.issued2024
dc.departmentFenerbahçe Universityen_US
dc.department-temp[Kulabas, Necla] Marmara Univ, Fac Pharm, Dept Pharmaceut Chem, TR-34668 Haydarpasa, Istanbul, Turkiye; [Lee, Jin-Ching] Natl Sun Yat Sen Univ, Dept Marine Biotechnol & Resources, Kaohsiung, Taiwan; [Lee, Jin-Ching] Kaohsiung Med Univ, Dept Biotechnol, Kaohsiung, Taiwan; [Ozakpinar, Ozlem Bingol] Marmara Univ, Fac Pharm, Dept Biochem, TR-34668 Haydarpasa, Istanbul, Turkiye; [Kucukguzel, Ilkay] Fenerbahce Univ, Fac Pharm, Dept Pharmaceut Chem, TR-34758 Istanbul, Turkiyeen_US
dc.description.abstractHepatitis C (HCV) is a viral infection that leads to forms of acute and chronic liver disease, including cirrhosis (scarring of the liver) and liver cancer. The World Health Organization (WHO) estimated in 2019 that approximately 290,000 people died from hepatitis C (mostly from cirrhosis and hepatocellular carcinoma). Directacting antiviral drugs (DAAs) can cure more than 95% of individuals with hepatitis C infection, while research on the discovery of new antiviral agents is still ongoing. The Hepatitis C virus (HCV) can cause various biochemical changes in liver cells, and some of these changes are associated with the COX-2 enzyme. The identification of its role in promoting growth in liver cells as well as its involvement in various cancer types, including hepatocellular carcinoma, has made COX-2 an important target in the development of new agents effective against HCV. In this study, thirty-six new 5-arylmethylene-2-imino-1,3-thiazolidin-4-one derivatives (5a-s, 6a-s) were synthesized through Knoevenagel condensation of 2-[(4-substitutedpyridin-2-yl)imino]-1,3thiazolidin-4-one derivatives with various aldehydes. Structures of the synthesized compounds were elucidated by the use of spectral and chromatographic techniques, besides elemental analyses. Four compounds were selected for further studies as they were found to suppress the NS5B protein with anti-HCV activity using the Western Blotting method. The selected compounds 5o, 6m, 6r, and 6s inhibited HCV with EC50 values of 8.0 +/- 0.2 mu M, 13.9 +/- 0.45, 9.2 +/- 0.2 mu M, and 12.1 +/- 0.1 mu M, respectively. It was determined that these compounds reduced HCV-induced COX-2 promoter activity in Ava5 cells compared to Huh7 cells. The antiviral effects of the compounds were also investigated on DENV, closely related to HCV due to sharing certain biological, structural, and mechanical properties throughout their life cycles. However, no significant effect was observed in the preliminary screening study, indicating the compounds' specificity for HCV. Considering the relationship between HCV, DENV, and COX-2, the compounds' COX-1 and COX-2 enzyme inhibition potentials were investigated both in vitro and in silico. Compounds 6d, 6e, 6f, and 6m, which exhibited high selective COX-2 inhibition, were discussed for their interactions with the active site. Our study revealed that our target compounds suppressed COX-2 both at the protein level and through enzyme inhibition, thus providing promising findings for the discovery of new anti-HCV effective COX-2 inhibitors.en_US
dc.description.sponsorshipScientific Research Project Commision of Marmara University [SAG-C-DRP-050614-0227]; Ministry of Science and Technology of Taiwan [MOST111-2311-B-110-001]; Scientific and Technological Research Council of Turkey (TUBITAK) [2211-C]en_US
dc.description.sponsorshipThis study was supported by the Scientific Research Project Commision of Marmara University (Project number: SAG-C-DRP-050614-0227) and the Ministry of Science and Technology of Taiwan (under grant numbers MOST111-2311-B-110-001). Necla Kulabas also thanks to the Scientific and Technological Research Council of Turkey (TUBITAK) for Domestic PhD Scholarship intended for Priority Areas (Code: 2211-C).en_US
dc.description.woscitationindexScience Citation Index Expanded
dc.identifier.citation0
dc.identifier.doi10.1016/j.molstruc.2024.138407
dc.identifier.issn0022-2860
dc.identifier.issn1872-8014
dc.identifier.scopus2-s2.0-85191714624
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://doi.org/10.1016/j.molstruc.2024.138407
dc.identifier.urihttps://hdl.handle.net/20.500.14627/219
dc.identifier.volume1311en_US
dc.identifier.wosWOS:001238241600001
dc.identifier.wosqualityQ2
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.scopus.citedbyCount0
dc.subject4-Thiazolidinonesen_US
dc.subjectHepatitis C Virusen_US
dc.subjectDengue Virusen_US
dc.subjectNs5Ben_US
dc.subjectDockingen_US
dc.subjectAntiviral Activityen_US
dc.subjectEnzyme Inhibitorsen_US
dc.titleSynthesis and Anti-Hcv Activity of Novel 5-Arylmethylene Derivatives Via Suppression of Ns5b Polymerase and Cox-2en_US
dc.typeArticleen_US
dc.wos.citedbyCount0
dspace.entity.typePublication
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