Novel 4-((3-fluorobenzyl)oxy)benzohydrazide derivatives as promising anti-prostate cancer agents: Synthesis, characterization and in vitro & in silico biological activity studies

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dc.contributor.authorÇakır, Furkan
dc.contributor.authorAteşoğlu, Şeyma
dc.contributor.authorKöse, Aytekin
dc.contributor.authorGhaffari-Moghaddam, Mansour
dc.contributor.authorAkbaş, Fahri
dc.contributor.authorKuran, Ebru Didem
dc.contributor.authorUlusoy Güzeldemirci, Nuray
dc.contributor.authorKılınç, Namık
dc.contributor.authorTokalı, Feyzi Sinan
dc.contributor.authorŞenol, Halil
dc.date.accessioned2025-04-16T12:34:30Z
dc.date.available2025-04-16T12:34:30Z
dc.date.issued2025
dc.departmentSabire Yazıcı Fen Edebiyat Fakültesi
dc.description.abstractIn this study, ten novel halogenated arylidenehydrazide derivatives were synthesized and characterized through 1H, 13C APT, 19F NMR, HSQC, HMBC, HRMS, and FT-IR techniques. Cytotoxic evaluations against PC3 prostate cancer and HUVEC cell lines identified compounds 8 and 14 as lead candidates, achieving IC50 values of 4.49 mu M and 4.78 mu M, respectively, with notable selectivity indexes of 12.15 and 11.78, underscoring their specificity against PC3 cells. Molecular docking studies targeting AR, VEGFR1, EGFR, and VEGFR2 suggested potential inhibitory mechanisms, with compounds 8 and 14 displaying substantial binding affinities for AR and VEGFR1. Compound 8 achieved IFD scores of -12.900 kcal/mol for AR and -10.895 kcal/mol for VEGFR1, while compound 14 recorded scores of -10.323 kcal/mol and -10.379 kcal/mol, respectively. Complementary MM-GBSA analyses revealed favorable binding energies, with compound 8 yielding Delta G values of -76.60 kcal/mol (AR) and -78.08 kcal/mol (VEGFR1) and compound 14 showing -80.67 kcal/mol (AR) and -78.61 kcal/mol (VEGFR1). MD simulations confirmed complex stability over 50 ns, indicating that compound 14 exhibited enhanced binding stability with key residues in AR and VEGFR1. ADME predictions highlighted drug-like properties, particularly for compounds 8 and 14, with high lipophilicity and favorable absorption characteristics, despite low aqueous solubility. SAR analysis emphasized the beneficial impact of halogen substitutions on potency and selectivity, establishing compounds 8 and 14 as promising candidates for further therapeutic development.
dc.description.sponsorshipMolecular Dynamics
dc.identifier.doi10.1016/j.molstruc.2024.140702
dc.identifier.issn0022-2860 / 1872-8014
dc.identifier.issue4
dc.identifier.urihttps://dx.doi.org/10.1016/j.molstruc.2024.140702
dc.identifier.urihttps://hdl.handle.net/20.500.12451/13065
dc.identifier.volume1322
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.institutionauthorKöse, Aytekin
dc.language.isoen
dc.publisherElsevier
dc.relation.ispartofJournal of Molecular Structure
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectHydrazide
dc.subjectHydrazone
dc.subjectMTT
dc.subjectProstate Cancer
dc.subjectMolecular Docking
dc.titleNovel 4-((3-fluorobenzyl)oxy)benzohydrazide derivatives as promising anti-prostate cancer agents: Synthesis, characterization and in vitro & in silico biological activity studies
dc.typeArticle

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