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- ArticleYalnız künye2027Synthesis, structural characterization, and in vitro and in silico anticancer evaluation of chalcone-based heterocyclic and boron difluoride derivatives
Serdaroğlu, Vildan; Demir, Fatma; Aydın, Ali; Türkmenoğlu, Burçin; Kahriman, Nuran
In this research, a series of novel bioactive heterocyclic polar compounds were designed and synthesized by incorporating various functional groups to enhance their biological and functional properties. The work involved the synthesis of chalcone (1–9, 10–18), boron difluoride complex (19–21), pyrazoline (22–25), and pyrimidine (26–37) compounds with their structures characterized through spectral techniques including NMR (1H, 13C (APT), 1H–1H COSY), FT-IR spectroscopies, LC-MS spectrometry. The anticancer potential of all compounds was assessed using lung cancer cell lines (A549, Calu1, H1650), brain cancer cell lines (A172, C6, B35), as well as normal lung (Beas2B) and chondrocyte (HC) cell lines. Compounds exhibiting a GI50 value below 3.0 µg/mL and a TGI value under 100 µg/mL were classified as having anticancer activity, based on comparisons with the reference drug 5-fluorouracil (5FU). Overall, compounds 24, 34, and 36 emerged as the most promising lead candidates by combining potent antiproliferative activity, favorable GI50-derived selectivity indices, and low toxicity toward normal cells, whereas compounds 2, 32, and 35 demonstrated the highest overall biological potency across multiple cancer cell lines. Representative GI50 values as low as 1.0–1.2 µg/mL, TGI values as low as 1.3–2.5 µg/mL, and LC50 values generally exceeding 500 µg/mL in normal cell lines were obtained in the most responsive models, supporting the potential of these derivatives for further anticancer development. To support these detailed in vitro studies, the most active compounds targeting TP53, EGFR, Akt1, mTOR, ERK2, and caspase 3, which are effective in lung and brain cancer pathways, were interacted via in silico molecular docking. Through molecular docking, the interaction values of compounds 2, 6, 7, 8, 13, 14, 17, 18, 24, 27, 32, 35, 36, and 37 with the determined targets were calculated, and their potential as promising lead candidates for drug development was analyzed.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2026Novel Imino Derivatives of Thymol: Synthesis, in vitro Cytotoxic Activities, Molecular Docking Analysis and ADME Prediction
Başaran, Eyüp; Türkmenoğlu, Burçin; Akkoc, Senem
Cancer is a significant global health challenge that affects millions of individuals every year. The development of new anticancer drugs is imperative to address the issue of drug resistance in cancer therapy. Therefore, in this study, novel imino derivatives of thymol (3a-c) were synthesized and evaluated as anticancer agents. These compounds were structurally elucidated using elemental analysis and various spectroscopic methods, including 1H and 13C Nuclear Magnetic Resonance (NMR) and Fourier Transform Infrared Spectroscopy (FT-IR). The cytotoxic activities of the new compounds on human liver cancer (HepG2) and healthy human kidney (HEK-293T) cell lines were investigated. Compounds were tested at various concentrations to determine their IC50 values. Among the tested new compounds, 3a and 3b demonstrated cytotoxicity in HepG2, with IC50 values of 88.97 µM and 106.10 µM, respectively. Furthermore, compound 3a also exhibited significant toxicity against the HEK-293T cell line, suggesting that further modifications are needed to improve selectivity for healthy cells. ADME properties analysis resulted in the detection of two lead compounds (3a and 3b) among compounds 2a-c and 3a-c. For the most active compounds 3a and 3b, molecular docking study on epidermal growth factor tyrosine kinase receptor (PDB ID: 3POZ), PI3K alpha (PDB ID: 4FA6), c-kit tyrosine kinase (PDB ID:1T46) was performed to verify the in vitro experimental results.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2026Design, synthesis, and computational studies of pyridine-substituted 1,2,3-triazoles with anticancer and antibacterial activities
Dilitatlı, Sümeyye; Demirbanka, Fatma Gül Özçelik; Türkmenoğlu, Burçin; Köse, Muhammet
A new series of pyridine-based 1,2,3-triazole derivatives (SD5–7) was synthesized through Cu(I)-catalyzed azide–alkyne cycloaddition and fully characterized by FT-IR, NMR, HRMS, and elemental analysis. The molecular structures of SD6 and SD7 were further confirmed by single-crystal X-ray diffraction, which revealed stabilizing π–π stacking and weak intermolecular interactions. Additionally, the properties of compounds SD5, SD6, and SD7 were investigated by density functional theory using B3LYP/6-311G*. Cytotoxic properties were investigated against OUMS (cancerous) and HUVEC (healthy) cell lines using MTS assays. SD5 exhibited the most potent effect on OUMS cells (IC50 = 98.05 µg/mL), exceeding the activity of cisplatin, while SD6 displayed statistically significant selectivity between cancer and normal cells. Antibacterial screening against Gram-positive (S. aureus, B. cereus) and Gram-negative (E. coli, K. pneumoniae) strains showed that SD5 and SD6 had moderate inhibitory effects (MIC = 5 mg/mL), whereas SD7 was inactive. These results suggest that pyridine-substituted 1,2,3-triazoles represent valuable scaffolds with promising dual anticancer and antibacterial potential for further development. Compounds SD5–7 exhibited cytotoxic effects against the OUMS cell line within the concentration range of 98.05–876.0 µg/mL, while in antibacterial tests, the ligands showed lower activity compared to streptomycin. SD5 and SD6 compounds, whose activity was determined in vitro studies, were analyzed to elucidate the interaction mechanism with the targets identified in molecular docking studies. Compounds SD5 and SD6 were analyzed in molecular docking studies by interacting with the crystal structures of 5I96 and 6U4J.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2026Inhibitory effect of Vaccinium arctostaphylos L. and Vaccinium myrtillus L. extracts on melanogenesis in α-MSH-induced B16F10 melanoma cells: in vitro, molecular docking ADMET and drug-likeness studies
Güven, Zühal Bayrakçeken; Türkmenoğlu, Burçin
BACKGROUND: Vaccinium species are characterised by high nutritional value and rich phytochemical composition of their fruits and are therefore used as food and in folk medicine. The aim of this study was to investigate the potential of fruits and leaves of the Vaccinium arctostaphylos L. and Vaccinium myrtillus L. for use as cosmeceuticals and against hyperpigmentation-related skin diseases. The antityrosinase and melanogenesis effects were determined by inhibition of mushroom tyrosinase enzyme, inhibition of tyrosinase enzyme in α-MSH (melanocyte-stimulating hormone)-induced B16F10 cells and melanin inhibition. RESULTS: The ethyl acetate sub-extract from the fruits of V. arctostaphylos showed very strong tyrosinase enzyme inhibition (median inhibitory concentration (IC50) = 9.71 μg mL−1), which was approximately as high as that of the standard compound, and also showed significant melanin inhibition and antityrosinase effect compared to kojic acid. The ethyl acetate extracts from the fruits and leaves of V. arctostaphylos showed antioxidant effect as strong as the standard compounds gallic acid and Trolox. The phytochemical contents of fruit and leaf extracts were analysed by liquid chromatography–tandem mass spectrometry (LC–MS/MS). ADMET (absorption, distribution, metabolism, excretion, and toxicity) profiles of the compounds were predicted and their likeness to drug candidates were analysed. Finally, molecular docking analysis was performed with the crystal structures of different targets determined for compounds (rutin, protocatechuic acid, gentisic acid, catechin, chlorogenic acid, caffeic acid, p-coumaric acid, taxifolin, salicylic acid, 4-hydroxybenzoic acid, luteolin-7-glycoside, quercetin). CONCLUSION: The fruit extracts of V. arctostaphylos in particular appear to be a potential and promising source for the cosmeceutical and pharmaceutical industry due to their content of active ingredients and strong biological effect.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2026Synthesis of Novel 4,6-Dimethoxyindole-Based Hydrazones Derived From 2,4-Dimethoxybenzaldehyde: Design, Cytotoxic Activity, Molecular Docking, and ADME-Tox Studies
Çakmak, Reşit; Başaran, Eyüp; Akkoç, Senem; Türkmenoğlu, Burçin; Köprü, Semiha; Bingül, Murat
In this study, a series of indolyl hydrazone derivatives (5–10) were designed and synthesized from 2,4-dimethoxybenzaldehyde (DMBA) (1) as potential chemotherapeutic agents. The structures of the synthesized compounds were confirmed by elemental analysis, FT-IR, 1D, and 2D NMR spectroscopy, and high-resolution mass spectrometry (HRMS). Their cytotoxic activities were evaluated against human breast (MCF-7), liver (HepG2), and colorectal (DLD-1) cancer cell lines. All compounds exhibited cytotoxic effects at micromolar concentrations, with IC50 values ranging from 8.97–26.07 µM for MCF-7, 22.50–70.99 µM for HepG2, and 5.93–66.31 µM for DLD-1 cells. Compound 10 demonstrated the strongest activity against MCF-7 and DLD-1 cells, with IC50 values of 8.97 ± 0.31 and 5.93 ± 0.11 µM, respectively. Compound 7 showed the highest antiproliferative activity against HepG2 cells (22.50 ± 1.23 µM), exceeding the activity of cisplatin (37.27 ± 2.42 µM). Molecular docking studies revealed favorable binding affinities of the most active compounds (7 and 10) toward selected targets. In addition, in silico ADME-toxicity analyses predicted acceptable physicochemical and pharmacokinetic properties, supporting the potential of these derivatives as promising anticancer candidates.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2026Synthesis and Biological Evaluation of New Thiocarbamoylpyrazoline and Chalcone Derivatives on Bone Cancer Cell Lines: In Vitro and In Silico Studies
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.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2026Pharmacologic Activation of TRPA1 Induces Multi-Target Anticancer Responses via Apoptotic and Mitochondrial Pathways
Çakır, Murat; Aydın, Ali; Türkmenoğlu, Burçin; Seçme, Mücahit
Objectives: Transient Receptor Potential Ankyrin 1 (TRPA1) has emerged as a stress-responsive ion channel involved in calcium homeostasis, redox signaling, migration, and cancer cell survival; however, the therapeutic relevance of TRPA1 activation versus inhibition remains poorly understood. In this study, we comparatively investigated the anticancer potential of the TRPA1 agonist ASP7663 and the TRPA1 antagonist HC030031 across a broad panel of human cancer cell lines. Methods: Antiproliferative and cytotoxic effects were evaluated using MTT and LDH assays, while apoptotic signaling, DNA fragmentation, mitochondrial membrane potential, migration inhibition, DNA/BSA interactions, topoisomerase I inhibition, and molecular docking analyses were comprehensively assessed. Results: ASP7663 exhibited markedly lower GI50 values than HC030031 in most cancer models and demonstrated favorable tumor selectivity relative to normal cells. Mechanistically, ASP7663 induced robust apoptotic activation characterized by significant upregulation of Caspase-3, Caspase-8, and Caspase-9, together with enhanced DNA fragmentation and pronounced nuclear condensation. Rhodamine-123 staining further revealed substantial mitochondrial membrane depolarization, indicating activation of intrinsic apoptotic pathways. In addition, ASP7663 produced selective membrane damage in malignant cells, stronger inhibition of migration in osteosarcoma and chondrosarcoma models, enhanced CT-DNA/BSA binding affinity, partial topoisomerase I inhibition, and superior docking interactions with apoptosis-related targets, including Caspase-3, Caspase-8, Caspase-9, Bax, and Bcl-2. Conclusions: Collectively, these findings suggest that ASP7663 is a promising multi-target candidate for anticancer therapy and support further investigation of TRPA1-associated pathways as potential therapeutic targets in cancer.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2026Dual-Function Schiff Base/Nitro-Phenanthroline Cu(II), Co(II), and Mn(II) Complexes: Exploring Cytotoxic Activity, Catalytic Efficiency, and Molecular Docking Insights
Sarıoğlu, Ahmet Oral; Sogukomerogullari, Hatice Gamze; Türkmenoğlu, Burçin; Taşdemir, Demet; Aytar, Emine; Sürmelihindi, Bahar; Alyamaç, İbrahim Tahsin
This study reports the synthesis and characterization of mixed-ligand Cu(II), Co(II), and Mn(II) complexes derived from 2-(((2-hydroxyphenyl)imino)methyl)-4-methoxy-6-nitrophenol (L1) and 5-nitro-1,10-phenanthroline (L2). The ligand and complexes were characterized by 1H/13C NMR (L1 only), FT-IR, UV–vis, LC-MS/MS, TGA, and elemental analysis. Cytotoxicity studies against A549 and HTB-54 lung cancer cells identified the Cu(II) complex as the most active compound, with IC50 values of 24.05 and 22.08 µM, respectively, while showing lower toxicity toward BEAS-2B normal cells (IC50 = 39.08 µM). The Cu(II) complex significantly inhibited cell migration and induced apoptosis, supported by increased Bax expression in qPCR analysis. Molecular docking with selected cancer-related protein targets further supported its proposed anticancer mechanism. The catalytic activity of the complexes was investigated for the solvent-free cycloaddition of CO2 with epoxides. The Co(II) complex exhibited the highest catalytic performance, affording 86.5% yield and 97.0% selectivity in the presence of DMAP under optimized conditions. Density functional theory (DFT) calculations provided the EHOMO, ELUMO, chemical potential, hardness, softness, electrophilicity index, and MEP profile of the ligand and complexes, demonstrating their multifunctional potential for anticancer and sustainable catalytic applications.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2026In vitro and in silico investigation of the cytotoxic potential of Tanacetum armenum (DC.) Sch.Bip. Extracts against human breast cancer MCF-7 cells
Güven, Zühal Bayrakçeken; Barlak, Neslişah; Türkmenoğlu, Burçin; Karadayı, Mehmet; Yilmaz, Mustafa Abdullah; Dilek, Esra; Inceer, Huseyin; Cakir, Oguz
Introduction: The genus Tanacetum has a long history of use and is well known for its traditional applications in food, medicine, cosmetics, and agriculture. The biological effects of Tanacetum armenum were investigated, and its phytochemical profiles were analysed. Methods: Phytochemical analysis was conducted using liquid chromatography-mass spectrometry/mass spectrometry, and antioxidant, target enzyme inhibition, and antigenotoxic effects were evaluated. The antiproliferative effects and mechanisms of the extracts were investigated in vitro, and the possible mechanisms of the main compounds were analysed in silico. Results: Phytochemical profile analysis revealed significantly higher levels of chlorogenic acid (64.894 mg/g extract), quinic acid (45.377 mg/g extract), and 1,5-dicaffeoylquinic acid (18.150 mg/g extract). The methanol extract (IC50:116.56 ± 2.84 µg/mL) exhibited strong tyrosinase enzyme inhibition than ethylacetate (IC50:184.04 ± 3.02 µg/mL) and aqueous extracts (IC50:340.84 ± 3.46 µg/mL). The aqueous extract (IC50:328.23 ± 4.22 µg/mL) showed the highest inhibition of acetylcholinesterase, while the methanol extract (IC50:504.87 ± 4.78 µg/mL) demonstrated the highest inhibition of butyrylcholinesterase. The ethylacetate extract exhibited the strongest antimicrobial effect against Staphylococcus aureus, with a MIC value of 62.5 µg/mL. The extracts did not show any genotoxic effects. The ethyl acetate extract exhibited significant cytotoxic effects (IC50:25.00–108.16 µg/mL) against cancer cell lines (p < 0.001). To investigate the mechanism by which the extracts inhibit MCF-7 cell viability, the expression levels of the cyclin E1 and caspase-8 were evaluated using western blot analysis. In addition, a colony formation assay was performed, and migration potential was analysed using a scratch wound healing assay. Using in silico approaches, the molecular docking and binding parameter values of cyclin E1 and caspase-8 were calculated. Chlorogenic acid was found to have the best binding value and mode of in silico interaction with the target crystal structures. The docking scores calculated from these binding parameter values were -7.824 kcal/mol for the cyclin E1 (8H6P) target, -7.126 kcal/mol for the caspase-8 (3KJQ) target, and -8.182 kcal/mol for the human oestrogen receptor (3ERT) target. Conclusion: T. armenum, which has demonstrated a strong cytotoxic effect through in vitro and in silico mechanism studies, can be considered a promising potential natural resource for cancer treatment.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2026Design, Synthesis, and Biological Evaluation of Methoxy-Substituted Chalcones and Gypsogenin-Based Hybrids as Anticancer and Antimicrobial Agents
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.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2026A study of the synthesis, characterization, cytotoxicity assessment, and molecular docking of Cu(II), Ni(II), and Co(II) ions with Schiff base and 1,10-phenanthroline
Sarıoğlu, Ahmet Oral; Törer, Hakan; Taşdemir, Demet; Türkmenoğlu, Burçin; Alyamaç, İbrahim Tahsin; Sönmez, Mehmet
This work covers the synthesis, cytotoxicity evaluation, and molecular docking study of new metal complexes formed by the coupling of 2-(((2-hydroxyphenyl)imino)methyl)-4-nitrophenol (L1) and 1,10-phenanthroline (L2) ligands. The ligand (L1) and its mixed ligand complexes with Cu(II), Co(II), and Ni(II) salts were analyzed using elemental analysis, FT-IR, TGA, UV-Vis, LC-MS/MS, NMR (just for the ligand L1), and magnetic susceptibility assessments. To our knowledge, this is the first report evaluating the cytotoxic and apoptotic effects of these complexes on A549 lung carcinoma and SH-SY5Y neuroblastoma cells. Among all synthesized compounds, copper complexes ([Cu(L1)(L2)H₂O] and [Cu(L1)2(H₂O)2]) exhibited significant cytotoxicity with IC50 values of 14.18 µM and 5.17 µM in A549 cells, and 37.96 µM and 23.35 µM in SH-SY5Y cells, respectively. Annexin V/PI apoptosis assays confirmed that the copper complexes induced both early and late apoptosis more effectively than cisplatin in A549 cells. Molecular docking studies further validated these findings, revealing strong interactions of copper complexes with B-DNA, EGFR, VEGFR-2, and ERK2, consistent with the observed anticancer activities. These results suggest that Cu(II)–Schiff base complexes represent promising lead compounds for future anticancer drug development.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2026Facile Synthesis and Characterization of Copper Hybrid Nanoflowers Using β-hydroxyamide–based Compounds: Investigation of their Anticancer Activity and Molecular Docking Analysis
Arslan, Nevin; Yılmaz, Burcu Somtürk; Özkan, Ahmet İsmail; Gültekin, Deniz Canbolat; Işık, Uğur; Azizoğlu, Murat; Türkmenoğlu, Burçin; Turgut, Yılmaz
Flower-like structures known as organic–inorganic hybrid nanoflowers (hNFs) are nanostructures that can be produced by combining organic and inorganic components. In this study, β-hydroxyamide–based compounds were used to synthesize copper hybrid nanoflowers (CuhNFs), and their in vitro cytotoxic activities were evaluated. The synthesized CuhNFs were characterized using SEM, EDX, elemental mapping, FT-IR, and XRD analyses to determine their morphological and structural properties. Cytotoxic effects were assessed on A549 lung cancer cells using the MTT assay. Among the tested samples, NM3-CuhNFs and NM5-CuhNFs exhibited the highest cytotoxicity at 125 μg/mL, with 24% and 32.5% inhibition, respectively. Overall, copper hybrid nanoflowers demonstrated greater cytotoxic activity than the parent β-hydroxyamide compounds. Cell viability decreased in a concentration-dependent manner. Based on these findings, NM3 and NM5 were further analyzed through molecular docking studies against EGFR, caspase-8, and PI3Kα. Both compounds showed favorable interactions with the selected targets, and their binding modes were elucidated in silico. These results indicate that β-hydroxyamide–derived copper hybrid nanoflowers may serve as promising candidates for the development of novel therapeutic strategies against lung cancer. This study represents the first report on the fabrication and biological evaluation of hybrid nanoflowers derived from β-hydroxyamide-based compounds. Future more comprehensive in vitro and in vivo studies are required to confirm the therapeutic efficacy and safety profile.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2026Development of pyridazinone derivatives linked ethyl-bridged-1,2,4-triazole for potential cancer therapy
Bozbey Merde, İrem; Aykaç, Okan; Hepokur, Ceylan; Yaşa, Yaren Zişa; Taşkor Önel, Gülce; Türkmenoğlu, Burçin
A series of novel pyridazinone derivatives linked ethyl-bridged-1,2,4-triazole were synthesized starting from p-chloroacetophenone. The chemical structures of the compounds 5(a-f) were identified by 1HNMR, 13CNMR and LC-QTOF-MS analysis. In this study, the DDPH method was used to evaluate the antioxidant properties of the compounds. The anticancer activity of the compounds was investigated by MTT method in MCF-7, MDA-MB-231 and L929 cell lines. Gene expression levels of Bcl2, Bax and Casp9 genes were compared, and stages of cell death were determined with high accuracy by flow cytometry. Since compound 5a showed promising cytotoxic effects, molecular docking study was performed to support these results and binding values against Bcl2 anti-apoptotic (PDB ID: 6QGG), Bcl-2 (PDB ID: 4IEH) and tubulin regulation (PDB ID: 1SA0) targets were calculated.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2025Synthesis of Sulfonamide-Based Schiff Bases as Potent Anticancer Agents: Spectral Analyses, Biological Activity, Molecular Docking, ADME, DFT, and Pharmacophore Modelling Studies
Başaran, Eyüp; Çakmak, Reşit; Türkmenoğlu, Burçin; Akkoc, Senem; Köprü, Semiha
The current study focuses on the synthesis and characterization of six benzenesulfonamide-based Schiff base derivatives (7–12) with various electron-withdrawing and electron-donating substituents (−F, -CI, -Br, −CH3, and −OCH3) and the assessment of their antiproliferative activities against human lung (A549) and liver (HepG2) cancer cell lines using in vitro and in silico approaches. The structures of the synthesized compounds (7–12) were elucidated by elemental analysis and FT-IR, 1D (1H, 13C, APT, and DEPT-135), and 2D (HMQC and HMBC) NMR spectroscopies. The cytotoxic activities of the targeted compounds were determined at various concentrations against these cancer cell lines for 72 h, using the MTT method. The targeted molecules (7–12) demonstrated remarkable antiproliferative activities, with IC50 values ranging from 6.032–9.533 μM against the A549 cell line and 5.244–9.629 μM against the HepG2 cell line. These compounds showed activities at lower or very similar concentrations to cisplatin against the A549 cell line and at much lower concentrations than cisplatin against the HepG2 cell line. Among them, compounds 10 and 12 were found to be more effective against A549 and HepG2 cells, respectively, than cisplatin. These compounds were analyzed by interacting with the 1BNA, 4HJO, and 4ASD crystal structures in molecular docking studies. The docking score of 4ASD-compound 12 interaction was calculated as −4.045 kcal/mol, 4HJO-compound 10 interaction was calculated as −5.179 kcal/mol and 1BNA-compound 10 interaction was calculated as −8.571 kcal/mol and it was determined that these compounds were theoretically better than Cisplatin. In the present study, ADME data were estimated using the web tool SwissADME. With ADME, it was calculated that the logP value of compounds 7–12 was less than 5, the HBD number was 1, the HBA number was 7 or 8, and the molecular weight was less than 500. Properties such as the electrophilic index and chemical hardness of the designed compounds were examined by density functional theory (DFT) using B3LYP/6-311G**. In conclusion, these compounds have emerged as promising new anti-cancer drug candidates.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2025Biological evaluations and computational studies of newly synthesized thymol-based Schiff bases as anticancer, antimicrobial and antioxidant agents
Sahin, Dicle; Kepekci, Remziye Aysun; Türkmenoğlu, Burçin; Akkoc, Senem
Three new thymol-based molecules were synthesized and evaluated as anticancer, antimicrobial and antioxidant agents. Liver, colon, lung and prostate cancer cell lines were utilized in cytotoxicity tests. The results demonstrated that synthesized molecules had a cytotoxic effect against the screened cell lines. One of the molecules (4a) was found to have a higher efficacy towards the colon cancer cell line (DLD-1) with an IC50 value of 12.39 µM and the other (4c) towards the prostate cancer cell line (PC3) with an IC50 value of 7.67 µM than the positive control drug cisplatin. To assess the antimicrobial activity of molecules (4a–c), Gram-positive bacteria, Gram-negative bacteria and yeast were subjected to agar disc diffusion and broth microdilution assays. The investigation of antioxidant potential was conducted using the DPPH radical scavenging activity assay. While all compounds displayed strong cytotoxic and antioxidant properties, they exhibited only moderate antimicrobial activity. Molecular docking studies were performed on epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor 2 (VEGFR-2), focal adhesion kinase (FAK), B-Raf and phosphoinositide 3-kinase (PI3K). The binding energies and interactions obtained from the docking results of compounds (4a–c) supported the experimental results. Drug similarity rates and pharmacokinetic properties were analyzed with the absorption, distribution, metabolism and excretion (ADME) method. Geometric parameters such as chemical potential (µ), electrophilicity index (ω) and chemical softness (σ) of compounds (4a–c) were calculated using the 6-31*G basis set B3LYP method.
RDL Kalıcı Kaydıİncele - Review ArticleYalnız künye2025Design, spectroscopic characterization, in silico and in vitro cytotoxic activity assessment of newly synthesized thymol Schiff base derivatives
Başaran, Eyüp; Çakmak, Reşit; Sahin, Dicle; Köprü, Semiha; Türkmenoğlu, Burçin; Akkoc, Senem
Cancer is a global public health problem affecting millions of people every year. New anticancer drug candidates are needed to overcome the resistance to drugs used in the treatment of various types of cancer. In this study, two new series of benzenesulfonate-based thymol derivatives (14–19 and 20–25) were synthesized for the first time as promising chemotherapeutic agents and characterized using FT-IR, 1D NMR (1H- and 13C-NMR, APT, DEPT 135), 2D NMR (HETCOR and HMBC), and elemental analysis (CHNS). Antiproliferative activity of the molecules was determined against cancer cell lines, namely, the human lung adenocarcinoma cell line (A549) and the colorectal adenocarcinoma cell line (DLD-1), using MTT method for both 48 and 72 h. Compounds (14–25) showed cytotoxic activities against A549 with IC50 values ranging from 9.98 to 81.83 μM, respectively, compared to cisplatin (6.65 μM). These compounds exhibited antiproliferative activities against DLD-1 cancer cells at concentrations ranging from 4.29 to 53.62 μM, respectively, compared to cisplatin (9.91 μM). Especially, compound 16 displayed significant cytotoxicity on A549 and DLD-1 cancer cells with IC50 values of 9.98 and 10.75 μM, respectively. Finally, molecular docking studies were performed with Bcl-2, VEGFR-2, EGFR, and HER2 targets using the Schrödinger 2021-2 Maestro Glide program. The binding energy values and binding interactions of compounds 16 and 22 were determined to be the result of their interactions with these targets. Schrödinger 2021-2 Qikprop wizard drug similarity ratios and ADME prediction of all compounds 14–25 were also calculated.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2025Chalcone-based imidazo[2,1-b]thiazole derivatives: synthesis, crystal structure, potent anticancer activity, and computational studies
Dadou, Said; Altay, Ahmet; Baydere, Cemile; Anouar, El Hassane; Türkmenoğlu, Burçin; Koudad, Mohammed; Dege, Necmi; Oussaid, Abdelouahad; Benchat, Noureddine; Karrouchi, Khalid
In this work, two novel chalcone-based imidazothiazole derivatives ITC-1 and ITC-2 were synthesized and characterized by 1H NMR, 13C NMR and high-resolution mass spectrometry with electrospray ionization, and chemical structure of ITC-1 was confirmed by single-crystal X-ray diffraction. Also, the anticancer activity of ITC-1 and ITC-2 was evaluated. First, antiproliferative activity tests were performed against cancer cells namely, human-derived breast adenocarcinoma (MCF-7), lung carcinoma (A-549), and colorectal adenocarcinoma (HT-29) cell lines, and mouse fibroblast healthy cell line (3T3-L1) by XTT assay. Afterward, mitochondrial membrane disruption (MMP), caspase activity, and apoptosis tests were performed on MCF-7 cells to elucidate the anticancer mechanism of action of the test compounds by flow cytometry analysis. XTT results revealed that both compounds exhibited a very high degree of antiproliferative effects on each tested cancer cell line with very low IC50 values while showing much lower antiproliferation on 3T3-L1 normal cells with much higher IC50 values. Besides, ITC-2 was determined to have a striking cytotoxic power competing with the chemotherapeutic drug carboplatin. Flow cytometry results demonstrated the mitochondrial-mediated apoptotic effects of both compounds through membrane disruption and multi-caspase activation in MCF-7 cells. Finally, molecular docking studies were performed to determine the structural understanding of the test compounds by their interactions on caspase-3 and DNA dodecamer enzymes, respectively. The interactions between the compound and the crystal structure were determined according to parameters such as free binding energies (ΔGBind), Glide score values, and determination of the active binding site. The obtained data suggest that ITC-1 and ITC-2 may be considered remarkable anticancer drug candidates. In addition to molecular docking via in silico approaches, the pharmacokinetic properties of compounds ITC-1 and ITC-2 were calculated using the Schrödinger 2021-2 Qikprop wizard. Communicated by Ramaswamy H. Sarma.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2025Quantum Chemical Calculation, Molecular Docking, and Biological Activity Properties of Imidazole, Pyrimidine, and Diazepine Based Compounds
Akkoc, Senem; Çağlar-Yavuz, Sevtap; Türkmenoğlu, Burçin; Tuğrul Zeyrek, Celal; Ilhan, Ilhan Ozer; Alhag, Sadeq K.; Al-Shuraym, Laila A.
In this study, seven known compounds (5a–g) were tested towards four human cancer cell lines including DLD-1, HepG2, MDA-MB-231, and MCF-7 for 48 h. In addition, all compounds were also tested in a normal human cell line (Wl-38). The results showed that a compound 5e in particular had cytotoxic effects in DLD-1, HepG2, and MCF-7. The molecular modeled structures of seven investigated compounds 5a–g in the ground state were optimized using density functional theory (DFT). The chemical parameters were determined by DFT calculations. HOMOs and LUMOs of 5a–g were revealed to provide a reasonable qualitative indication of their excitation properties. To support experimental studies, compounds (5a, 5c, and 5e) with anticancer effects were interacted with epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor 2 (VEGFR-2), which were determined as possible targets. As a result of these interactions, binding parameter values (docking score, Glide e-model, Glide energy) between ligand and target were calculated.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2025Transition metal complexes of sulfonamide-based schiff base ligand: Synthesis, characterization, a biological assessment, DFT, and ADME studies
Sarıoğlu, Ahmet Oral; Türkmenoğlu, Burçin; Kahraman, Demet Taşdemir; Güler, Semih; Sürmelihindi, Bahar; Morcali, Mehmet Hakan
The present study examines the synthesis of Schiff bases through the reaction between 2‑hydroxy-5-nitrobenzaldehyde and sulfacetamide (N-(4-aminophenylsulfonyl)acetamide). The structure of the ligand and metal complexes (Cu+2, Ni+2, Co+2) was characterized using a variety of techniques, including elemental analysis, magnetic susceptibility, molar conductivity, UV–Vis, FT-IR, NMR, and LC-MS/MS. The cytotoxic effects of the complexes and ligand were tested on three cell lines: human epidermoid carcinoma (HTB-54), lung adenocarcinoma (A549), and neuroblast (SH-SY5Y). Furthermore, the antibacterial capabilities of Schiff base and its metal complexes were evaluated against a range of bacterial strains, including B. cereus and S. aureus, as well as resistant gram-positive and gram-negative bacteria like S. typhimurium and E. coli, and fungi like C. albicans. In the computational chemistry section, the physicochemical properties of the synthesized compounds, including EHOMO, ELUMO, ΔEGap, electrophilic index, chemical hardness, chemical potential, electrophilicity index, and chemical softness, were investigated using the B3LYP/6–31G* basis set of density functional theory (DFT).
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2025Design, synthesis of antipyrine-based Schiff bases and investigation of their cholinesterase and carbonic anhydrase activities by in vitro and in silico approaches
Çakmak, Reşit; Başaran, Eyüp; Türkmenoğlu, Burçin; Şentürk, Murat
In this study, a series of antipyrine-based Schiff bases (1–10) was designed, synthesized, and evaluated as potential inhibitors of various metabolic enzymes, including acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and human erythrocyte carbonic anhydrase I and II (hCA I and hCA II). The target molecules were characterized by UV–vis, FT-IR, 1H NMR, 13CNMR, LC-HRMS, and elemental analysis. All tested derivatives demonstrated low nanomolar inhibition with Ki values of in the range of 20.58 ± 0.35 to 53.11 ± 1.02 nM against AChE, 21.84 ± 0.40 to 54.41 ± 1.05 nM against BChE, 27.45 ± 0.41 to 48.22 ± 0.91 nM against cytosolic hCA I isoform associated with epilepsy, and 6.02 ± 0.11 to 29.32 ± 0.54 nM against cytosolic hCA II isoform associated with glaucoma. In general, most these molecules, except for a few, inhibited these enzymes more than acetazolamide (AZA) and neostigmine. Among them, compounds 5, 7, 8, and 9 showed the best inhibitory activities against AChE, BChE, hCA I, and hCA II, respectively. Docking results were calculated for the compounds that showed the best inhibitory activity against these enzymes and for reference compounds. Based on the molecular docking results, they were determined to have high binding energies, including hydrogen bonds, electrostatic interactions, and hydrophobic interactions. Absorption, distribution, metabolism, and excretion (ADME) parameters determined that all the synthesized pyrazolone ring-bearing Schif base derivatives (1–10) have the expected physicochemical properties in terms of drug-likeness and can be evaluated as orally active potential. Properties such as the electrophilicity index and chemical hardness were also investigated by density functional theory (DFT) at the B3LYP/6–311G** level of theory.
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