New quinazolinone-thiazolidinedione hybrids as selective anti-lung cancer agents and promising EGFR inhibitors.
1/5 보강
[AIM] Lung cancer remains a leading cause of cancer-related deaths, largely due to therapy resistance and toxicity.
APA
Tokalı P, Şenol AM, et al. (2026). New quinazolinone-thiazolidinedione hybrids as selective anti-lung cancer agents and promising EGFR inhibitors.. Future medicinal chemistry, 18(4), 415-428. https://doi.org/10.1080/17568919.2026.2620368
MLA
Tokalı P, et al.. "New quinazolinone-thiazolidinedione hybrids as selective anti-lung cancer agents and promising EGFR inhibitors.." Future medicinal chemistry, vol. 18, no. 4, 2026, pp. 415-428.
PMID
41636324 ↗
Abstract 한글 요약
[AIM] 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.
[MATERIALS AND METHODS] 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.
[RESULTS] Several compounds showed selective cytotoxicity against A549 cells, with compound 9 (thiophen-2-ylmethyl substituent) emerging as the most active (IC = 3.85 μM, SI = 36.0), outperforming gefitinib (IC = 9.59 μM, SI = 1.9) and exhibiting higher selectivity than sorafenib (IC = 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.
[CONCLUSION] These findings indicate that the synthesized hybrids, particularly compound , represent promising leads for selective EGFR-targeted lung cancer therapy and support further optimization.
[MATERIALS AND METHODS] 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.
[RESULTS] Several compounds showed selective cytotoxicity against A549 cells, with compound 9 (thiophen-2-ylmethyl substituent) emerging as the most active (IC = 3.85 μM, SI = 36.0), outperforming gefitinib (IC = 9.59 μM, SI = 1.9) and exhibiting higher selectivity than sorafenib (IC = 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.
[CONCLUSION] These findings indicate that the synthesized hybrids, particularly compound , represent promising leads for selective EGFR-targeted lung cancer therapy and support further optimization.
🏷️ 키워드 / MeSH 📖 같은 키워드 OA만
- Humans
- ErbB Receptors
- Antineoplastic Agents
- Quinazolinones
- Thiazolidinediones
- Lung Neoplasms
- Protein Kinase Inhibitors
- Molecular Docking Simulation
- Drug Screening Assays
- Antitumor
- Cell Proliferation
- Structure-Activity Relationship
- Molecular Structure
- Cell Line
- Tumor
- Molecular Dynamics Simulation
- 4-dione
- EGFR
- Quinazolin-4(3H)-one
- cytotoxicity
- lung cancer
- thiazolidine-2
🏷️ 같은 키워드 · 무료전문 — 이 논문 MeSH/keyword 기반
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