Demir, Fatma; Kahriman, Nuran; Aydın, Ali; Türkmenoğlu, Burçin; Mandal, Emre; Emirdağ, Safiye

In the pursuit of multifunctional therapeutic agents, a new series of thiocarbamoylpyrazoline derivatives were synthesized starting from chalcones, and all synthesized compounds (1–12) were structurally characterized using spectroscopic methods (NMR, FT-IR, and Q-TOF-LC-MS) and elemental analysis. The anticancer properties of the test compounds were evaluated in vitro against human bone cancer cell lines MG63 and SW1353 using MTT and LDH assays. LDH assay results demonstrated that the compounds exhibited no detectable cytotoxicity toward normal human chondrocyte (HC) cells. Compared to the reference drug 5-fluorouracil (5-FU), several compounds displayed notable antiproliferative activity. Tumor selectivity index (TSI) analysis identified compounds 1, 2, 4, and 10 as having high tumor selectivity, indicating a preferential cytotoxic effect toward cancer cells over normal cells. Among these, compounds 4 and 10 exhibited the most favorable anticancer profiles, combining potent antiproliferative activity with minimal toxicity to normal cells. Furthermore, to support the experimental anticancer findings, in silico molecular docking studies were performed using the crystal structures of caspase-3 (1GFW), human metalloproteinase-13 (3KEJ), human estrogen receptor (3ERT), and EGFR (1M17) against compounds 1, 2, 4, and 10, and their binding modes were analyzed.

Ulusoy, Nafia Gökçe; Emirdağ, Safiye; Kahriman, Nuran; Demir, Fatma; Serdaroğlu, Vildan; Yaylı, Nurettin; Türkmenoğlu, Burçin

Chalcones and natural product-based hybrids represent important scaffolds in the development of biologically active small molecules. In this study, a series of methoxy-substituted chalcone derivatives (1a–1i) and acetyl gypsogenin-based hybrid compounds (4a–4i) were synthesized and fully characterized by spectroscopic methods. The cytotoxic activities of all compounds were evaluated against five human cancer cell lines (PANC-1, MDA-MB-231, HeLa, A549, and SH-SY5Y) and the normal HEK293 cell line using the MTT assay. Several chalcone derivatives exhibited pronounced antiproliferative activity, whereas the corresponding gypsogenin-based hybrids generally showed reduced cytotoxic effects. Tumor selectivity was further assessed by calculating the selectivity index values. Antimicrobial activity was determined using minimum inhibitory concentration assays against selected bacterial and fungal strains, revealing moderate inhibitory effects for some compounds. In addition, molecular docking studies of the most active chalcones (1g and 1h) were performed to explore potential interactions with key cancer-related targets. Overall, the results highlight the chalcone scaffold as the main contributor to biological activity in this series and demonstrate that hybridization with gypsogenin did not enhance the cytotoxic potency.

Başaran, Eyüp; Köprü, Semiha; Akkoç, Senem; Türkmenoğlu, Burçin

In this study, we investigated the in vitro antiproliferative activities and performed computational studies of newly synthesized fluorinated isatin-hydrazones. The chemical structures of the synthesized compounds were confirmed by FT-IR, 1D NMR (1H- and 13C NMR and APT), 2D NMR (HETCOR and HMBC), and elemental analysis. All compounds (1-15) were tested in human lung (A549) and liver (HepG2) cancer cell lines for 72 h. The compounds were screened against a healthy embryonic kidney cell line (HEK-293T) under the same conditions to determine their toxic effects. According to the results obtained, one of the compounds, in particular, compound 8 was effective at inhibiting the growth of cancerous cells, and its effects on both cancer cell lines were similar to IC50 values of 42.43 and 48.43 μM for A549 and HepG2, respectively. Compound 8, which was determined to be the best anticancer agent in vitro, was chosen to interact with the target via molecular docking. This selected ligand (compound 8) interacted with the targets 4HJO, 4ASD, 3POZ, and 7TZ7, and docked into the active sites. The docking score, Glide energy, and Glide emodel values were calculated and determined to be lower than those of the reference compound cisplatin. The pharmacokinetic properties, stability, and drug-likeness parameters of all designed compounds were estimated using SwissADME. Finally, the binding affinities of compound 8 for all four targets were calculated using the MM-GBSA method.

Kaya, Betül; Acar Çevik, Ulviye; Çiftçi, Bilge; Duran, Hatice Esra; Türkeş, Cüneyt; Işık, Mesut; Bostancı, Hayrani Eren; Kaplancıklı, Zafer Asım; Beydemir, Şükrü

Inhibition ofaldose reductase (AR), α-glycosidase (α-GLY), and α-amylase (α-AMY) are some of the essential targets in diabetes mellitus (DM). Here, a series of imidazo[1,2-a]pyridine-based 1,3,4-thiadiazole derivatives (8a-k) were successfully synthesized and characterized using 1H NMR, 13C NMR, and HRMS spectroscopic techniques. The inhibition effects of the synthesized derivatives against AR, α-GLY, and α-AMY were evaluated using both in vitro and in silico methods. In vitro studies revealed that the derivatives (8a-k) showed significant inhibition activity. The results showed that the novel derivatives (8a-k) demonstrated potential inhibitory activity, with KI values covering the following ranges: 23.47 ± 2.40 to 139.60 ± 13.33 nM for AR and 6.09 ± 0.37 to 119.80 ± 12.31 μM for α-GLY, with IC50 values 81.14 to 153.51 μM for α-AMY. Furthermore, many of these compounds exhibited high inhibition activity, while some of them showed higher potency than the reference compounds. Molecular docking of the target compounds was carried out in the active sites of AR (PDB ID: 4JIR) and α-GLY (PDB ID: 5NN8).