Sürdürülebilir Kalkınma Amaçları

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• MakaleYalnız künye2026/r/kostu/10974
  Suppressing Liver Cancer via the VEGFR1 Receptor using De novo Ellagic Acid Derivatives and Co-drugs: Comprehensive In silico Biochemistry Research with ADMET, RMSD, Molecular Docking, and Molecular Dynamics Simulations

  Agar, S; Acar, E; Aldemir, O; Gokoluk, E; Issa, G; Bogdanov, J

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• MakaleAçık Erişim2026/r/kostu/10860
  In silico biochemical de novo drug design of valproic acid derivatives to suppress cancerous dna: comprehensive molecular docking, molecular dynamics, 1 h nmr, adme

  Acar, Esra; Issa, Ghassan; Agar, Soykan; Gökoluk, Erkan; Giglou, Erfan Akhavan; Şimşek, Dilruba

  Objective: This comprehensive in silico computational and theoretical biochemistry/organic chemistry research study covers the inhibition methodologies of 1-BNA, which is an essential template for cancer- suppressing research. By disrupting the minor groove domain binding site of the DNA template 1-BNA dodecamer, three de novo drug candidate molecules via derivatization of anti-epileptic valproic acid (VPA) drug were designed. Methods: Calf thymus DNA (ct-DNA) sequence d(CGCGAATTCGCG)2 dodecamer (PDB ID: 1BNA) was obtained from the Protein Data Bank to study. Molecular docking simulations, the most updated docking programs of AutoDock Vina and PyRx were utilized. Molecular dynamics (MD) simulations and Absorption, distribution, metabolism and excretion (ADME) analyses were employed by Schrödinger’s Desmond software. Results: Thorough in silico results of three new derivatized analogues of VPA showed that chloro-derivatized analogue with its -9.6 kcal/mol docking score and 297.2 µM inhibition constant (IC) has a much better indication in the suppression where isopropyl and fluoro derivatized analogues possess -9.1 kcal/mol docking score with 483.8 µM IC and - 8.3 kcal/mol docking score with 896.2 µM IC respectively compared to the results of pristine VPA’s -8.2 kcal/mol docking score with 863.6 µM IC. Along with the detailed ADME results, isopropyl and chloro- derivatized ligands prove their worth of being a new drug candidate. Conclusion: All results proved that the de novo derivatives of VPA illustrate better docking scores (better suppression) along with better ICs and oral absorption percentage values, meaning that the analogues possess better indications compared to pristine VPA toward the suppression of cancerous cell template DNA.

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• MakaleAçık Erişim2026/r/kostu/10859
  Suppressing breast cancer via 2KS1 protein using biochemical de novo drug design and repurposing of valproic acid derivatives with better indications: comprehensive molecular docking, molecular dynamics simulations, 1H nmr, and admet estimations

  Agar, Soykan

  Objective: This comprehensive in silico computational and theoretical biochemistry/organic chemistry research study covers the inhibition methodologies of 2KS1, which is an essential template for breast cancer-suppressing research. Methods: To block the active site domain binding site of this protein, three de novo designed organic molecules by derivatizing Valproic Acid (VPA) were studied. Pharmacological organic chemistry effects of these analogues were enhanced to suppress 2KS1 better. The most recent molecular docking, molecular dynamics (MD), Proton Nuclear Magnetic Resonance (1H NMR), and Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) values showed that the derivatives of VPA exhibit better docking scores along with lower (better) inhibition constants and higher oral absorption percentage values compared to pristine VPA, meaning that the analogues possess better indications/pharmacological profiles. Results: The new drug candidate derivatives showed approximately 50 to 200 times inhibition constant efficiency (1/50th to 1/200th of the dose usage) in the affinity and suppression capability compared to pristine VPA. Conclusion: Being able to conduct such a crucial cancer study proves the fact that this study sheds light on the potential of new highly efficient drug molecules for future studies in terms of in vitro and in vivo for the suppression of breast cancer disease.

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• MakaleYalnız künye2026/r/kostu/10841
  Inhibiting liver cancer via the VEGFR1 receptor protein using in silico biochemistry de novo drug analogues of ellagic acid: comprehensive admet, rmsd, molecular docking, and molecular dynamics simulations

  Agar, Soykan

  Objective: Ellagic Acid, one of the well-known Pharmacognostic molecules, has been discovered to have great potential in its new derivatives to be used as drug candidates to suppress liver cancer via the VEGFR1 receptor mechanism. This study aimed to simulate (in silico biochemistry) design two novel derivatives of Ellagic Acid, a hydroxylated analogue and an Ellagic Acid–Quercetin co-drug, to improve inhibitory binding against the VEGFR1 receptor implicated in liver cancer angiogenesis. Methods: Three-dimensional ligand structures were built and optimized using density functional theory (DFT) with the B3LYP/6-31G(d,p) basis set. Molecular docking simulations were performed using AutoDock Vina 1.2.0. The most favorable poses were subjected to molecular dynamics (MD) simulations in Desmond Maestro 2024-2 under NPT conditions (310 K, 1.01 bar) with the OPLS 3.0 force field. Binding free energies were assessed using MM/GBSA calculations. Results: The pristine Ellagic Acid possesses -89.236 kJ/mol of binding energy in Molecular Dynamics, where its de novo Hydroxylated analogue and Ellagic Acid-Quercetin co-drug possess -105.319 kJ/mol, -147.214 kJ/mol, respectively. The inhibition constant values of the two new drugs are nine times higher compared to pristine Ellagic Acid, proving their efficacy with much less dosage usage in the binding of VEGFR1 receptor’s active site. Conclusion: In two analogues of Ellagic Acid, results are so much better that they prove their worth from the perspective of in silico simulation studies in terms of being used as a VEGFR1 liver cancer transmembrane receptor inhibitor. Thus, these new molecules shed light on further in vitro cell line toxicity and in vivo studies for the future.

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• Derleme MakaleYalnız künye2026Scopus SJRQ2/r/kostu/10672
  Indomethacin as a Multi-target Anticancer Agent via Transmembrane Receptor-mediated Tumor Suppression: The Need for de novo Drug Derivatization

  Ozturk, Ebru; Issa, Ghassan; Agar, Soykan

  Introduction: Indomethacin, a non-steroidal anti-inflammatory drug (NSAID), has attracted increasing attention for its promising anticancer properties, particularly regarding its crucial effect on transmembrane receptor-mediated signal transduction in different cancers. Besides COX-inhibitory activities, other mechanisms underlying indomethacin's potential as an anticancer agent are being explored, including those related to the mediation of prostaglandin signaling through transmembrane receptors in solid tumors. Methods: In this mini-review, we summarize available information about modulation of transmembrane receptor signaling by indomethacin, including death receptors, EP receptors, receptor tyrosine kinases (RTKs), chemokine receptors, cannabinoid receptors, ACE2, P2X7, IP, and FZD/LRP5/6 receptors associated with Wnt pathways. Results: The presented data indicate that indomethacin may inhibit PGE₂-induced EP signaling, affect EGFR/FGFR and CXCR3 signaling pathways, increase death receptor-mediated apoptosis, and influence various types of receptor cross-talk involved in proliferation, angiogenesis, immune evasion, invasion, and metastasis. However, the most consistent results were obtained in colorectal cancer cells, while the role of indomethacin in breast, ovarian, and prostate cancers appears to be more contextual and receptor-profile dependent. Discussion: Overall, our review suggests that indomethacin functions mainly as a receptor signaling modulator rather than a selective receptor antagonist. The potential clinical application of indomethacin for cancer treatment is hindered by its poor selectivity towards COX enzymes, toxicity, and lack of specificity. Conclusion: Despite the possibility of using indomethacin as a template structure for creating more selective drugs, it seems that indomethacin cannot serve as a drug for anticancer therapy alone. This conclusion specifically positions parent indomethacin as a chemically modifiable scaffold for rational derivative development rather than as a final therapeutic endpoint. 2026, Bentham Science Publishers

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• MakaleYalnız künye2026Scopus SJRQ3/r/kostu/10559
  Investigating the interactions of Axitinib, a tyrosine kinase inhibitor, with DNA: experimental studies, molecular docking, and molecular dynamics simulations

  Şenel, Pelin; Faysal, Abdullah Al; Agar, Soykan; Yurtsever, Mine; Gölcü, Ayşegül

  Axitinib is an oral medication classified as a second-generation tyrosine kinase inhibitor. It serves as a primary treatment for metastatic renal cell carcinoma (RCC) due to its strong affinity for DNA, which leads to the disruption of the double helix structure. This disruption ultimately halts the cell cycle and induces senescence and mitotic catastrophe in RCC cells. Consequently, investigating the mechanism by which Axitinib binds to DNA is essential for comprehending its pharmacodynamic properties and for the advancement of more effective DNA-binding therapeutics. The present study aimed to examine the interaction between Axitinib and DNA through various analytical techniques, including UV-Vis spectroscopy, thermal denaturation assays, electrochemical methods, and fluorescence emission spectroscopy. According to the electrochemical studies, the binding constant (Kb) for Axitinib was calculated to be (5.13 ± 0.28) × 104, suggesting the potential for groove binding. This finding was further supported by in-silico analyses, where molecular docking and molecular dynamics simulations indicated that the drug selectively binds to the DNA minor groove through partial intercalation, forming new hydrogen bonds with its functional groups while separating the guanine and cytosine base pairs.

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  AtıfScopus1·WoS1·OpenAlex2

  İncele
• MakaleYalnız künye2026Scopus SJRQ2/r/kostu/10445
  Transition-metal coordination modulates predicted DNA groove recognition and nucleobase contacts in oligohistidine complexes

  Agar, Soykan; Yildiz, Alparslan Numan; Yurtsever, Mine

  Histidine-rich peptides are widely used in affinity-based purification because imidazole donors can coordinate transition-metal ions. To examine how fixed metal-coordination models may alter the predicted DNA-contacting behavior of a histidine hexamer, a fully in silico comparison was performed using metal-free His6 and the tri-metal model complexes [Zn3(His6)]6+, [Ni3(His6)]6+, and [Cu3(His6)]6+ against the canonical B-DNA dodecamer 1BNA [d(CGCGAATTCGCG)]. The formulas denote the neutral-terminal/neutral-imidazole computational representation used for docking and molecular dynamics (MD), rather than a claim concerning the dominant solution-phase species. Molecular docking and MD simulations were used to compare predicted groove localization, recurrent nucleobase-associated contacts, hydrogen-bond patterns, relative docking scores, and trajectory-based structural persistence. Within the examined 1BNA model, metal-free His6 produced a dominant major-groove pose with adenine-associated contacts and a Vina docking score of −8.9 kcal/mol. The tri-metal coordination models produced dominant minor-groove poses with guanine-associated contacts, with relative docking scores of −9.5, −13.5, and −10.8 kcal/mol for the Zn(II), Ni(II), and Cu(II) models, respectively. The Ni(II)- and Cu(II)-containing models also displayed lower RMSD levels than the metal-free complex over the sampled trajectories. These observations are restricted to the defined computational models and the 1BNA sequence; they do not establish experimental binding affinities, universal nucleobase selectivity, or solution-phase metal speciation. The work provides a hypothesis-generating comparison that may guide future experimental investigation of metal-coordinated oligohistidine-DNA interactions.

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• MakaleYalnız künye2025Scopus SJRQ2/r/kostu/10776
  An in-depth study of clofarabine's binding mechanism to DNA: A thorough experimental and theoretical investigation

  Agar, Soykan; Senel, Pelin; Al Faysal, Abdullah; Gölcü, Aysegul; Yurtsever, Mine

  The interaction of medicinal compounds with nucleic acids is a critical challenge in drug development. This research focused on the binding dynamics of clofarabine (CLO), an antineoplastic agent, with fish sperm DNA (dsDNA) under conditions that simulate the physiological environment at a pH of 7.4. The investigations employed multiple techniques, including fluorescence and UV spectroscopy, thermal denaturation analysis, viscosity measurements, electrochemical assessments, and molecular docking studies to elucidate these binding interactions. The binding constant (Kb) for the interaction between CLO and dsDNA, as determined from the Benesi-Hildebrand plot, was found to be 2.74 x 104 at a temperature of 298 K. The entropy (Delta S) and enthalpy (Delta H) changes associated with this binding interaction were measured as + 43.08 J mol- 1 K- 1 and -12.44 kJ mol-1, respectively. These values indicate that the predominant forces driving the binding interaction are primarily due to hydrogen bonding. Studies using the ethidium bromide and the Hoechst probe showed that CLO does not bind to dsDNA intercalatively. Findings obtained through UV-Vis absorption spectroscopy, competitive binding assays, and viscosity assessments indicated that CLO associates with dsDNA by binding within the minor groove. Molecular docking analyses demonstrated that CLO is accommodated within the ATrich segment of the minor groove, with significant hydrogen bonding interactions occurring between CLO and dsDNA. These findings may offer valuable perspectives for elucidating the mechanisms underlying the toxicity, resistance, and adverse effects associated with CLO.

  AtıfWoS3·OpenAlex4

  İncele
• MakaleYalnız künye2025Scopus SJRQ3/r/kostu/10422
  De novo Drug Design and Repurposing to Suppress Liver Cancer via VEGF-R1 Mechanism: Comprehensive Molecular Docking, Molecular Dynamics Simulations and ADME Estimation

  Agar, Soykan

  Aim: The aim is to halt the progression of liver cancer (Hepatocellular carcinoma) by suppressing the VEGF-R1 receptor using Myricetin and its de novo-designed analogues. Background: VEGF/VEGFR autocrine signalling promotes the growth, progression, and metastasis of Hepatocellular carcinoma, making the development of molecularly targeted therapies highly feasible. Invasive and metastatic behaviours in various cancers, including hepatocellular carcinoma (HCC), are closely monitored through the use of VEGF signalling pathway inhibitors. Specifically in HCC, VEGFR-1 facilitates the invasive capabilities of cancer cells primarily by triggering the epithelial-mesenchymal transition (EMT) process. VEGFR-1 significantly influences the activity of proteolytic enzymes that are critical for the invasive behaviour of HCC cells. Notably, a novel mechanism has been discovered where VEGFR-1 activation leads to the upregulation of MMP-9, thereby enhancing the invasiveness of HCC cells. The scientists, in their study, have elaborated on the various antiangiogenic agents developed for the treatment of HCC. They have highlighted clinical trials that explore the efficacy of these treatments, which include the application of monoclonal antibodies and small-molecule kinase inhibitors designed to target specific pathways involved in tumour angiogenesis and growth. Objective: Creating a pharmaceutical chemistry table regarding “Structure-Activity Relationship of New Compounds on anticancer”. To do so, Myricetin and its de novo designed structured variants were used in molecular docking, molecular dynamics, cluster analyses, and 1H NMR estimation to specifically understand and enhance the mechanism of suppressing the VEGF-R1 receptor. Methods: Proper ligands (Myricetin and its analogues) and receptor (VEGF-R1) preparations, and optimizations were done using the density functional theory (DFT)/B3LYP function along with the 6-31G(d,p) basis set principle in the latest software programs such as Gaussian 09, Gauss View 6.0 and Avogadro. Then using PyRx and Autodock Vina 1.1.2., many molecular docking trials were achieved with 100 posed simulations in each run. An extensive cluster analysis was performed to identify the most optimal docking poses with the highest accumulation and most favourable binding interactions, ensuring the accuracy of the study. The docking configurations that exhibited the most precise and accurate poses with lowest inhibition constants were chosen as initial structured data for subsequent Molecular Dynamics (MD) simulations for each drug candidate. To verify the molecular docking results, MD runs were achieved in our supercomputers and the trajectory analyses were made. The data confirmed what was found in molecular docking results, verifying the high efficiency of the druggable molecules’ inhibition towards VEGF-R1. Results: Amine-derivatized Myricetin has a significantly high docking score (-10.56 kcal/mol) and great inhibition constant compared to pristine Myricetin (-4.77 kcal/mol) itself while Fluorine-derivatized Myricetin (-6.45 kcal/mol) has an affinity towards VEGF-R1 between the first two molecules. Thus, the structure-activity relationship concerning pharmaceutical chemistry aspects of all the molecules studied, yielded us a great insight into what Myricetin’s organic structure possesses towards inhibiting the progression of Liver Cancer. Also, ADME studies showed that both Amine and Fluorined-derivatized Myricetin molecules are good drug candidates. Conclusion: This study highlighted the significant potential of Myricetin as an anti-cancer drug when modified with specific functional groups. Through comprehensive in silico computational analyses, our research group enhanced Myricetin's inhibitory capabilities by derivatizing its Hydroxyl group with Amine and Fluorine, resulting in improved docking scores and inhibition constants. The findings from molecular docking and MD simulations provide a promising foundation for future in vitro and in vivo investigations of these molecules as potential drugs in cancer research.

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  AtıfScopus3·WoS5·OpenAlex8

  İncele
• DüzeltmeAçık Erişim2025Scopus SJRQ3/r/kostu/10383
  Erratum to: CORRECTION TO: The Inhibition Mechanism of Pancreatic Ductal Adenocarcinoma via LXR Receptors: A Multifaceted Approach Integrating Molecular Docking, Molecular Dynamics and Post-MD Inter-Molecular Contact Analysis (Asian Pacific Journal of Cancer Prevention, (2023), 24(12), (4103), (10.31557/APJCP.2023.24.12.4103))

  Demirag, Aliye Demet; Agar, Soykan

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