Browsing by Author "Deniz, Elif"

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Design, Synthesis, and Evaluation of Benzoxazole-Linked Pyrazole Hybrids as VEGFR-2 Antiproliferative Agents
(Humana Press inc, 2025) Deniz, Elif; Coven, Furkan Ozan; Erguc, Ali; Karakus, Fuat; Kuzu, Burak
In this study, a series of benzoxazole-linked pyrazole compounds (20a-t) were synthesized and tested for their antiproliferative activity. Their effects on lung cancer (A549) and normal lung (CCD-34Lu) cell lines were evaluated using the MTT assay. Among them, compounds 20m and o showed strong antiproliferative effects, with IC50 values of 7.64 and 15.82 mu M, respectively, and selectivity indices of 2.84 and 1.95 in favor of cancer cells. ELISA tests demonstrated that both compounds statistically significantly reduced VEGFR-2 protein levels by 24.8 and 28.7% at their respective IC50 values, indicating potential antiangiogenic properties. Molecular docking studies supported these findings by showing favorable binding of 20m and o to the VEGFR-2 receptor, with binding energies of -7.33 kcal/mol and -7.22 kcal/mol, respectively. Overall, compounds 20m and o stand out as promising candidates for further development as anticancer drugs.
Potential Inhibitors of Extra-Synaptic Nmdar/Trpm4 Interaction: Screening, Molecular Docking, and Structure-Activity Analysis
(Elsevier, 2023) Deniz, Elif; Karakus, Fuat; Kuzu, Burak
Over-activation of extra-synaptic NMDARs by excessive glutamate is known to cause excitotoxicity. The molecular mechanism of how this excitotoxicity occurs was revealed recently. This paper presents the results of in silico studies aimed at finding potential small-molecule inhibitors that can block this mechanism, namely the extra-synaptic NMDAR/TRPM4 interaction. We screened for small molecules according to 2D (at least Tanimoto threshold was 90%) and/or 3D similarity, molecular weight, lipophilicity using control compounds (C8 and C19) targeting this interaction. We then pre-filtered these molecules according to their drug-likeness and toxicity profiles. After pre-filtering, we performed a docking study against the extra-synaptic NMDAR/TRPM4 interaction with the remaining 26 compounds. In addition, we determined that selected compounds exhibit low affinity for classical NMDAR ligand binding sites. Ultimately, we identified four novel compounds (C8-12, C8-15, C19-3, C19-4) that could block the extra-synaptic NMDAR/TRPM4 interaction without inhibiting the normal function of synaptic NMDARs.