Furkan Çakır

Lung cancer remains a leading cause of cancer-related deaths, largely due to therapy resistance and toxicity. This study develops novel quinazolinone-thiazolidinedione (TZD) hybrids by combining two anticancer pharmacophores to achieve more selective and potent EGFR inhibitors. A total of 14 quinazolinone-TZD hybrids were synthesized and characterized. Their cytotoxicity was evaluated in A549 lung adenocarcinoma and BEAS-2B normal bronchial cells. EGFR binding was analyzed via molecular docking and MM-GBSA, with 500 ns molecular dynamics simulations supporting the stability of selected complexes. ADME predictions assessed drug-likeness and oral bioavailability. Several compounds showed selective cytotoxicity against A549 cells, with compound 9 (thiophen-2-ylmethyl substituent) emerging as the most active (IC₅₀ = 3.85 μM, SI = 36.0), outperforming gefitinib (IC₅₀ = 9.59 μM, SI = 1.9) and exhibiting higher selectivity than sorafenib (IC₅₀ = 3.24 μM, SI = 5.4). Computational analyses revealed key interactions with EGFR residues (Cys-797, Arg-841, Asn-842, and Phe-997), supported by stable molecular dynamics behavior and favorable ADME predictions. These findings indicate that the synthesized hybrids, particularly compound 9, represent promising leads for selective EGFR-targeted lung cancer therapy and support further optimization.

A new series of thiosemicarbazone derivatives were synthesized and evaluated as dual α-Glu/α-Amy inhibitors.

The aim of this study is to design, synthesize, and characterize novel benzo [f] chromene‐substituted thiosemicarbazone derivatives as potential anticancer agents, based on the rationale of simultaneously targeting key cancer‐related enzymes and signaling pathways to improve therapeutic efficacy against lung cancer. For these purposes, 18 novel thiosemicarbazone derivatives 4a–r were synthesized. Among them, compound 4p exhibited the most promising anticancer effects against A549 cells, with an IC ₅₀ value of 5.11 µM and a selectivity index (SI) of 10.55, surpassing the reference drug sorafenib. Compound 4p also demonstrated potent enzyme inhibitory activity, particularly against hCA I (IC ₅₀ = 104.26 nM) and hCA II (IC ₅₀ = 95.18 nM), outperforming acetazolamide. In anticancer assays, compound 4p (SI = 10.55) was about twice as effective as sorafenib (SI = 5.34), and in enzyme inhibition, it showed ~1.5‐fold greater potency than acetazolamide. Molecular docking studies show strong binding interactions of 4p with hCA I, hCA II, and BRAF, with favorable docking scores and stable protein–ligand complexes confirmed by 100‐ns and 250‐ns triplicate random seed MD simulations. Additionally, pharmacokinetic predictions indicated excellent drug‐like properties for 4p , including high permeability, oral absorption, and adherence to Lipinski's rule. These findings highlight compound 4p as a promising candidate for an anticancer agent targeting key enzymes involved in lung cancer progression.

Five novel 1,2,3‐triazole/arylidenehydrazide/thiazolidinone hybrid compounds ( 7–11 ) were synthesized and characterized using NMR, HRMS, IR, and HPLC purity analysis. The cytotoxicity of these compounds was evaluated on fibroblasts and THP‐1 cells, showing that all compounds were nontoxic at the tested concentrations. The wound healing assay revealed that compounds 7 , 9 , and 10 significantly enhanced wound closure, with a 7.74%–32.69% improvement in treated cells. Compounds 8 and 11 showed moderate effects. Anti‐inflammatory activity was assessed through qRT‐PCR, demonstrating that compound 10 led to the most significant reduction in proinflammatory cytokines TNF‐α, IL‐1β, and NF‐κB1. In addition, the expression of Iba1 protein in THP‐1 cells confirmed that compound 8 showed the strongest anti‐inflammatory effect, surpassing that of aspirin. Compound 10 showed the highest inhibition of NF‐κB signaling and iNOS activity. Molecular docking studies revealed that compounds 10 and 11 had strong binding affinities to TNF‐α and iNOS, with compound 11 showing the most stable interactions. Molecular dynamics simulations supported these findings, indicating that compound 11 demonstrated more stable binding to both targets. Overall, the results suggest that compounds 10 and 11 are promising anti‐inflammatory candidates with potential for further development in therapeutic applications for inflammatory diseases.

Twenty‐one novel quinazolin‐4(3 H )‐one derivatives were synthesized and evaluated for their cytotoxic effects against the PC3 prostate cancer cell line. Structural characterization was performed using FTIR, NMR, and HRMS spectroscopy. Cytotoxicity assays revealed that compound 1 exhibited the highest potency (IC ₅₀ = 4.29 ± 0.32 µM) and selectivity (SI = 20.1) against PC3 cells, surpassing the reference drug sorafenib. Compounds 10 and 11 also demonstrated significant selectivity (SI = 12.7 and 12.4, respectively), making them promising candidates for further investigation. Molecular docking studies confirmed strong binding affinities to the androgen receptor (AR), with compound 1 displaying the most favorable interaction (IFD Glide Score = −15.137 kcal/mol, MM‐GBSA = –72.11 kcal/mol). MD simulations further supported the stability of compound 1 within the receptor binding site, highlighting key hydrogen bonding and π–π stacking interactions. ADME predictions indicated favorable pharmacokinetic properties, with all active compounds complying with drug‐likeness criteria and exhibiting high oral absorption. Overall, these findings suggest that quinazolinone derivatives, particularly compound 1 , hold significant potential as selective anticancer agents targeting prostate cancer.