Unraveling mechanism and enhancing selectivity of a RuII‐bis‐bipyridyl‐morphocumin complex with RAFT‐generated glycopolymer exploiting Warburg effect in cancer DOI
Arindam Mukherjee, Souryadip Roy, Soumya Paul

et al.

Chemistry - A European Journal, Journal Year: 2024, Volume and Issue: 31(8)

Published: Nov. 30, 2024

The Warburg effect, which generates increased demand of glucose in cancer cells is a relatively underexplored phenomenon existing commercial drugs to enhance uptake cells. Here, we present chemotherapeutic strategy employing Ru(II)-bis-bipyridyl-morphocumin complex (2) encapsulated self-assembling glucose-functionalized copolymer P(G-EMA-co-MMA) (where G=glucose; MMA=methyl methacrylate; EMA=ethyl methacrylate), designed exploit this effect for enhanced selectivity treatment. polymer, synthesized via reversible-addition fragmentation chain transfer (RAFT) polymerization, has number average molecular weight (Mn,NMR) 8000 g/mol. Complex 2, stable aqueous media, selectively releases cytotoxic, lysosome-targeting compound, morphocumin, the presence excess hydrogen peroxide (H₂O₂), reactive oxygen species (ROS) prevalent tumor microenvironments. Additionally, 2 promotes ROS accumulation, may further morphocumin release through synergistic domino effect. Comparative studies reveal that outperforms its curcumin Ru(II) (1) analog solution stability, organelle specificity, and cellular mechanisms. Both 1 exhibit phototherapeutic effects under low-intensity visible light, but their chemotoxicity significantly increases with incubation time dark, highlighting superior efficacy O,O-coordinating ternary polypyridyl complexes. induces apoptosis intrinsic pathway shows 9-fold increase pancreatic (MIA PaCa-2) over non-cancerous HEK293 when glucose-conjugated polymer (DP@2). Glucose deprivation culture medium enhances drug by an additional 5-fold. This work underscores potential polymers ROS-responsive complexes targeted therapy.

Language: Английский

A series of quinazolin‐4(3H)‐one‐morpholine hybrids as anti‐lung‐cancer agents: Synthesis, molecular docking, molecular dynamics, ADME prediction and biological activity studies DOI
Feyzi Sinan Tokalı, Halil Şenol, Şeyma Ateşoğlu

et al.

Chemical Biology & Drug Design, Journal Year: 2024, Volume and Issue: 104(1)

Published: July 1, 2024

Abstract In this study, we synthesized 15 novel quinazoline‐morpholinobenzylideneamino hybrid compounds from methyl anthranilate and assessed their cytotoxicity via in vitro assays against A549 BEAS‐2B cell lines. Molecular docking studies were conducted to evaluate the protein‐ligand interactions inhibition mechanisms on nine different molecular targets, while dynamics (MD) simulations carried out assess stability of best docked ligand–protein complexes. Additionally, ADME prediction was determine physicochemical parameters drug likeness. According assays, compound 1 (IC 50 = 2.83 μM) found be most active inhibitor cells. While selectivity index (SI) is 29, SI reference drugs paclitaxel sorafenib, used are 2.40 4.92, respectively. Among compounds, has scores VEGFR1 (−11.744 kcal/mol), VEGFR2 (−12.407 kcal/mol) EGFR (−10.359 kcal/mol). During MD simulations, consistently exhibited strong hydrogen bond with sites 2, these maintained for more than 90% simulation time. RMSD RMSF values complexes high at minimum levels around 1–2 Å. conclusion, findings suggest that may a potent selective candidate lung cancer treatment VEGFR2, especially.

Language: Английский

Citations

10
Synthesis of pyrrole-heterocyclic derivatives as anti-Alzheimer and antidiabetic candidates: An in vitro-in silico study DOI
О. В. Петрова, Denis N. Tomilin, Halil Şenol

et al.

Journal of Molecular Structure, Journal Year: 2024, Volume and Issue: 1315, P. 138998 - 138998

Published: June 14, 2024

Language: Английский

Citations

8
Synthesis, biological evaluation, and in silico studies of phenyl naphthalene-2-sulfonate derived thiosemicarbazones as potential carbonic anhydrase inhibitors DOI

Javeria Eshal,

Hafiza Zara Tariq, Jing Li

et al.

Bioorganic Chemistry, Journal Year: 2025, Volume and Issue: 155, P. 108118 - 108118

Published: Jan. 4, 2025

Language: Английский

Citations

1
Synthesis and Biological Studies of Acetophenone-Based Novel Chalcone, Semicarbazone, Thiosemicarbazone and Indolone Derivatives: Structure-Activity Relationship, Molecular Docking, Molecular Dynamics, and Kinetic Studies DOI

Aynur Farzaliyeva,

Halil Şenol, Parham Taslımı

et al.

Journal of Molecular Structure, Journal Year: 2024, Volume and Issue: 1321, P. 140197 - 140197

Published: Sept. 26, 2024

Language: Английский

Citations

4
Exploring anticancer properties of new triazole-linked benzenesulfonamide derivatives against colorectal carcinoma: Synthesis, cytotoxicity, and in silico insights DOI
Belma Zengin Kurt, Özge Özmen, Dilek Öztürk Civelek

et al.

Bioorganic & Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 119, P. 118060 - 118060

Published: Jan. 5, 2025

Language: Английский

Citations

0
Necroptotic Suppression of Lung Cancer Cell Proliferation and Migration: A Comprehensive In Vitro and In Silico Study to Determine New Molecular Targets for Pexidartinib DOI
Ebru Hacıosmanoğlu, Dilraj Lama, Hande İpek Yetke

et al.

Cell Biochemistry and Function, Journal Year: 2025, Volume and Issue: 43(3)

Published: March 1, 2025

ABSTRACT In this study, the cytotoxic effects of pexidartinib (PLX), a tyrosine kinase inhibitor approved for tenosynovial giant cell tumor through inhibition colony‐stimulating factor 1 receptor (CSF1R), against A549 lung adenocarcinoma cells and Beas‐2B healthy bronchial were investigated by in detailed in‐vitro in‐silico studies. Through MTT assays, PLX demonstrated significant viability with IC 50 values 2.15 1.3 µM at 24 48 h, respectively, while having minimal on cells, 36.2 9.3 µM. The high selectivity index indicates PLX's preferential action cancerous cells. mechanism death induced was further explored using Annexin V/PI staining flow cytometry, revealing that primarily induces necrosis an increase necrotic populations reduced efficacy higher concentrations. Western blot analysis showed upregulation necroptosis markers (RIP3 pMLKL) apoptotic like Caspase‐3 remained unchanged. addition, wound healing assays significantly inhibits migration dose‐dependent manner. Molecular docking studies identified key amino acids involved binding interactions target proteins. RIPK1 strongest affinity. MD simulations revealed PLX‐VEGFR2 complex most stable. As conclusion, PLX, although tumors, shows promising potential treatment. It selectively cancer viability, necroptosis, reduces migration. Its stronger to VEGFR2 more than CSF1R.

Language: Английский

Citations

0
Synergistic Antiproliferative Activity of Newly Synthesized Benzimidazole-Based Silver(I) Complexes on MCF-7 and T47D Cell Lines, CT-DNA Interactions Supported by Computational Studies DOI Creative Commons

Naima Munir,

Nevın Gürbüz, Gul-e-Saba Chaudhry

et al.

ACS Omega, Journal Year: 2025, Volume and Issue: unknown

Published: March 28, 2025

This article reports the synthesis, characterization, and antitumor properties of newly synthesized benzimidazole-based Ag(I)-(BNHCs) complexes from their proligands. All compounds underwent comprehensive characterization using techniques such as 1H, COSY, 13C NMR, IR spectroscopy, electrospray ionization (ESI)-mass, elemental, single-crystal X-ray diffraction (XRD) analysis. Density functional theory (DFT) studies were carried out to observe electronic effects bound ligands modulate selectivity reactivity silver complexes. Time-dependent DFT (TD-DFT) assessed optical further highlighted by orbital contributions with oscillator strengths. tested against breast cancer MCF-7 T47D cell lines. The synergistic benzimidazole-incorporated aryl constituent structuring also observed. Nearly all have been found be promising anticancer agents added benefit low cytotoxic toward normal cells. Intriguingly, [AgL 4 (Cl)] exhibited best activity among our screened IC50 values for both 9 ± 1.04 11 1.41, respectively. apoptosis mode death was confirmed phosphatidylserine exposure annexin V/PI staining imaging method. CT-DNA interactions most active complex ([AgL (Cl)]) its proligand (HL (Cl)) support compound-DNA interaction. Strong DNA binding affinities (K b) through electrostatic intercalation modes induced structural changes in DNA. Moreover, molecular docking comprehend possible various receptors EGFR (epidermal growth factor receptor), VEGFR2 (vascular endothelial receptors), FGFR (fibroblast SRC (proto-oncogene tyrosine kinase protein) family serves crucial cancer.

Language: Английский

Citations

0
Inhibition Effects of Some Phenolic Anthraquinone Derivatives on Lactoperoxidase Activity: A Detailed in Vitro and in Silico investigation DOI Creative Commons
Işıl Nihan Korkmaz, Halil Şenol, Ramazan Kalın

et al.

Food Biophysics, Journal Year: 2025, Volume and Issue: 20(2)

Published: April 11, 2025

Language: Английский

Citations

0
LC‐MS and GC‐MS Analyses on Green Algae Penicillus capitatus: Cytotoxic, Antimicrobial and Anticholinesterase Activity Screening Enhanced by Molecular Docking & Dynamics and ADME Studies DOI
Gülbahar Özge Alim Toraman, Sezen Atasoy, Halil Şenol

et al.

Chemistry & Biodiversity, Journal Year: 2024, Volume and Issue: unknown

Published: July 11, 2024

In this comprehensive screening study, the chemical composition, and cytotoxic, antimicrobial, anticholinergic activities of green algae Penicillus capitatus, collected from Antalya-Türkiye, were determined as in vitro silico. GC-MS analysis hexane extract revealed a high content fatty acids, with hexadecanoic acid constituting half total content. LC-HRMS DCM:MeOH identified ascorbic most abundant compound, followed by (-)-epigallocatechin salicylic acid. The exhibited potent cytotoxicity against MDA-MB-231 MCF7 breast cancer cell lines, outperforming doxorubicin lower IC

Language: Английский

Citations

2
Novel 4-((3-fluorobenzyl)oxy)benzohydrazide Derivatives as Promising Anti-Prostate Cancer Agents: Synthesis, Characterization and in vitro & in silico Biological Activity Studies DOI
Furkan Çakır, Şeyma Ateşoğlu, Aytekin Köse

et al.

Journal of Molecular Structure, Journal Year: 2024, Volume and Issue: 1322, P. 140702 - 140702

Published: Nov. 10, 2024

Language: Английский

Citations

2