Novel Benzimidazole-Oxadiazole Derivatives as Anticancer Agents with VEGFR2 Inhibitory Activity: Design, Synthesis, In Vitro Anticancer Evaluation, and In Silico Studies

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dc.authoridcelik, ismail/0000-0002-8146-1663
dc.contributor.authorCevik, Ulviye Acar
dc.contributor.authorCelik, Ismail
dc.contributor.authorGorgulu, Sennur
dc.contributor.authorInan, Zeynep Deniz Sahin
dc.contributor.authorBostanci, Hayrani Eren
dc.contributor.authorKarayel, Arzu
dc.contributor.authorOzkay, Yusuf
dc.date.accessioned2025-05-04T16:46:58Z
dc.date.available2025-05-04T16:46:58Z
dc.date.issued2025
dc.departmentSivas Cumhuriyet Üniversitesi
dc.description.abstractThe aim of this research is the synthesis of benzimidazole-1,3,4-oxadiazole derivatives that could be potential anticancer leads inhibiting VEGFR2. The compounds were evaluated for their cytotoxicity against cancer cell lines PANC-1, MCF-7, and A549 using the MTT assay. Two different normal cell lines (hTERT-HPNE and CCD-19Lu) were used to calculate the selectivity indices of the compounds. Compound 4r showed the highest anticancer activities, with IC50 = 5.5, 0.3, and 0.5 mu M against the PANC-1, A549, and MCF-7 cell lines, respectively. Also, compounds 4r and 4s were further evaluated for their inhibitory activity against VEGFR2. VGFRA immunolocalizations of compounds 4r and 4s were visualized by the VEGFA immunofluorescent staining method. Molecular docking studies have proven that, as in sorafenib, compounds 4r and 4s show hydrogen bond formation with Asp1046 and Cys919 and hydrophobic interactions with other active site amino acids. Molecular dynamics simulations were carried out for compounds 4r and 4s to examine the stability and behavior of the protein-ligand complex obtained from molecular docking under in silico physiological conditions. An in silico ADME investigation was undertaken to confirm the druglikeness of the synthesized compounds. Furthermore, the stable geometries of the ligands were determined through the application of density functional theory (DFT). The optimized geometries were confirmed to correspond to true minima, as no imaginary frequencies were observed in the vibration frequency survey. The rotations of the thio and benzimidazole groups with respect to the 1,3,4-oxadiazole rings are 180 deg, and the molecules are planar.
dc.description.sponsorshipAnkara Universitesi [BAP-21B0237004]; BAGEP Award of the Science Academy
dc.description.sponsorshipThis work was supported by the BAGEP Award of the Science Academy. Schrodinger software was purchased with Ankara University-Scientific Research Unit to provide grant project number BAP-21B0237004. This paper's molecular dynamics numerical calculations were partially performed at TUBITAK ULAKBIM in TURKEY, High Performance and Grid Computing Center (TRUBA resources).
dc.identifier.doi10.1021/acsomega.4c08885
dc.identifier.endpage6813
dc.identifier.issn2470-1343
dc.identifier.issue7
dc.identifier.pmid40028103
dc.identifier.scopus2-s2.0-85217788907
dc.identifier.scopusqualityQ1
dc.identifier.startpage6801
dc.identifier.urihttps://doi.org/10.1021/acsomega.4c08885
dc.identifier.urihttps://hdl.handle.net/20.500.12418/35432
dc.identifier.volume10
dc.identifier.wosWOS:001422594100001
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherAmer Chemical Soc
dc.relation.ispartofAcs Omega
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WOS_20250504
dc.subjectExchange
dc.titleNovel Benzimidazole-Oxadiazole Derivatives as Anticancer Agents with VEGFR2 Inhibitory Activity: Design, Synthesis, In Vitro Anticancer Evaluation, and In Silico Studies
dc.typeArticle

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