Akademik Veri Yönetim Sistemi
Journal of Molecular Structure, cilt.1360, 2026 (SCI-Expanded, Scopus)
Colorectal, liver, and uterine cancers remain major clinical challenges due to their high prevalence and mortality. In this study, a series of artesunate-benzofuran hybrid compounds (5A-5E) were designed and synthesized through a multistep approach and structurally characterized by 1H/13C NMR, FTIR, and LC-MS/MS analyses. Their anticancer and anti-inflammatory potential was evaluated using complementary in silico and in vitro methodologies. Drug-likeness and ADMET predictions indicated favorable pharmacokinetic behavior and low toxicity. Molecular docking studies demonstrated strong binding affinities toward key cancer-related targets, DNA polymerase β (POLB), caspase-8 (CASP8), and protein kinase A (PKA), with binding energies ranging from -91.66 to -170.97 a.u., exceeding those of tamoxifen (TAM) (-88.40 to -114.88 a.u.) and 5-fluorouracil (5FU) (-52.27 to -53.79 a.u.). Molecular dynamics simulations further confirmed the stability of the ligand-protein complexes. In vitro cytotoxicity assays against Caco-2, HepG2, and Ishikawa cell lines revealed selective anticancer activity with minimal toxicity. Compounds 5A and 5C displayed the most pronounced effects, with half maximal inhibitory concentration (IC50) values of 51.48 µM (Caco-2) and 35.16 µM (HepG2) for 5A, and 58.32 µM (Caco-2) and 50.98 µM (HepG2) for 5C. Mechanistic investigations showed apoptosis induction via caspase activation, inhibition of cell migration, G0/G1 cell-cycle arrest, and suppression of colony formation. In addition, compounds 5A-5C significantly reduced lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophages. These results support artesunate-benzofuran hybrids as promising multitarget candidates for the development of anticancer agents with concurrent anti-inflammatory activity.