---
title: "Thiazole-hydrazone hybrids as targeted agents for non-small cell lung cancer"
id: "pubmed-42612271"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42612271"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42612271/"
doi: "10.1016/j.bioorg.2026.110369"
published_at: "2026-10-05T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Thiazole-hydrazone hybrids as targeted agents for non-small cell lung cancer
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42612271
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42612271/)
- **DOI:** [10.1016/j.bioorg.2026.110369](https://doi.org/10.1016%2Fj.bioorg.2026.110369)
- **Published At:** 2026-10-05T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- The study synthesized a series of novel **thiazolyl hydrazones (2a–2t)** and evaluated them as targeted cytotoxic agents against non-small cell lung cancer (NSCLC) using the A549 human lung adenocarcinoma cell line and L929 mouse fibroblast cells. - Compound 2b showed the greatest cytotoxicity against A549 cells (IC50 = 6.10 µM) and was more potent than the reference EGFR tyrosine kinase inhibitor erlotinib (IC50 = 77.35 µM). - Multiple compounds (including 2g, 2k, 2r, 2f, 2o, 2e, 2s, 2h) also exceeded erlotinib in potency against A549 cells. - In vitro mechanistic assays indicated these molecules induce **apoptosis** and cause **G0/G1 cell cycle arrest**, implicating these processes in their cytotoxic effects. - Compound 2f was highlighted as the most promising lead for selective cytotoxicity via concurrent inhibition of **EGFR**, **Akt**, and **STAT3**, showing stronger inhibition of EGFR and STAT3 than erlotinib and the STAT3 inhibitor C188-9, respectively. - Compound 2e is reported as a potent dual **EGFR/STAT3 inhibitor**, with EGFR inhibition comparable to erlotinib and superior STAT3 inhibition versus C188-9. - Compound 2b’s primary mechanism was EGFR inhibition and it exhibited ~8.3-fold greater EGFR-targeted activity than erlotinib. - Compound 2r emerged as the most potent **STAT3** inhibitor in the series, with ~10.8-fold higher activity than C188-9. - Authors conclude that thiazolyl hydrazones warrant further investigation as targeted therapeutic candidates for NSCLC. No competing interests were declared by the authors.
## Clinical Analysis & Structured Key Points
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Epub 2026 Aug 11. # Development of thiazole-hydrazone hybrids for targeted therapy of non-small cell lung cancer [Mehlika Dilek Altıntop](https://pubmed.ncbi.nlm.nih.gov/?term=Alt%C4%B1ntop+MD&cauthor_id=42612271)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42612271/#full-view-affiliation-1 "Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey."), [İpek Ertorun](https://pubmed.ncbi.nlm.nih.gov/?term=Ertorun+%C4%B0&cauthor_id=42612271)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42612271/#full-view-affiliation-2 "Department of Biochemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey."), [Gülşen Akalın Çiftçi](https://pubmed.ncbi.nlm.nih.gov/?term=Akal%C4%B1n+%C3%87ift%C3%A7i+G&cauthor_id=42612271)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42612271/#full-view-affiliation-2 "Department of Biochemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey."), [Ahmet Özdemir](https://pubmed.ncbi.nlm.nih.gov/?term=%C3%96zdemir+A&cauthor_id=42612271)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42612271/#full-view-affiliation-3 "Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey. Electronic address: ahmeto@anadolu.edu.tr.") Affiliations Expand ### Affiliations * 1 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey. * 2 Department of Biochemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey. * 3 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey. Electronic address: ahmeto@anadolu.edu.tr. * PMID: **42612271** * DOI: [ 10.1016/j.bioorg.2026.110369 ](https://doi.org/10.1016/j.bioorg.2026.110369) Item in Clipboard # Development of thiazole-hydrazone hybrids for targeted therapy of non-small cell lung cancer Mehlika Dilek Altıntop et al. Bioorg Chem. 2026. Show details Display options Display options Format Abstract PubMed PMID Bioorg Chem Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Bioorg+Chem%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Bioorg+Chem%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42612271/) . 2026 Oct 5:181:110369. doi: 10.1016/j.bioorg.2026.110369. Epub 2026 Aug 11. ### Authors [Mehlika Dilek Altıntop](https://pubmed.ncbi.nlm.nih.gov/?term=Alt%C4%B1ntop+MD&cauthor_id=42612271)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42612271/#short-view-affiliation-1 "Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey."), [İpek Ertorun](https://pubmed.ncbi.nlm.nih.gov/?term=Ertorun+%C4%B0&cauthor_id=42612271)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42612271/#short-view-affiliation-2 "Department of Biochemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey."), [Gülşen Akalın Çiftçi](https://pubmed.ncbi.nlm.nih.gov/?term=Akal%C4%B1n+%C3%87ift%C3%A7i+G&cauthor_id=42612271)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42612271/#short-view-affiliation-2 "Department of Biochemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey."), [Ahmet Özdemir](https://pubmed.ncbi.nlm.nih.gov/?term=%C3%96zdemir+A&cauthor_id=42612271)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42612271/#short-view-affiliation-3 "Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey. Electronic address: ahmeto@anadolu.edu.tr.") ### Affiliations * 1 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey. * 2 Department of Biochemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey. * 3 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey. Electronic address: ahmeto@anadolu.edu.tr. * PMID: **42612271** * DOI: [ 10.1016/j.bioorg.2026.110369 ](https://doi.org/10.1016/j.bioorg.2026.110369) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID Linked Discoveries ## Abstract To identify targeted cytotoxic agents for the treatment of non-small cell lung cancer (NSCLC), novel thiazolyl hydrazones (2a-t) were synthesized and evaluated for their cytotoxicity toward A549 human lung adenocarcinoma and L929 mouse embryonic fibroblast cells. Among these compounds, compound 2b exhibited the highest cytotoxic activity against A549 cells (IC50= 6.10 µM), followed by compounds 2g, 2k, 2r, 2f, 2o, 2e, 2s, and 2h, all of which were more potent than erlotinib (IC50 = 77.35 μM). In vitro mechanistic assays were conducted to assess their effects on apoptosis, cell cycle, epidermal growth factor receptor (EGFR), Akt, and signal transducer and activator of transcription 3 (STAT3). Flow cytometry analyses revealed that these agents induced apoptosis and G0/G1 cell cycle arrest, indicating that their cytotoxic effects are mediated through these mechanisms. Compound 2f was identified as the most promising compound, exhibiting selective cytotoxicity mediated by the concurrent inhibition of EGFR, Akt, and STAT3, with greater inhibitory potency toward EGFR and STAT3 relative to the EGFR TKI erlotinib and the STAT3 inhibitor C188-9. Compound 2e emerged as a potent dual EGFR/STAT3 inhibitor, exerting EGFR inhibitory activity comparable to that of erlotinib while exhibiting superior STAT3 inhibitory activity relative to C188-9. Compound 2b showed the highest cytotoxic potency against A549 cells, primarily through EGFR inhibition, with 8.3-fold greater activity than erlotinib. Compound 2r was identified as the most potent STAT3 inhibitor, exerting 10.8-fold higher activity than C188-9. These findings highlight the potential of thiazolyl hydrazones as targeted therapeutic agents, warranting further investigations for NSCLC treatment. **Keywords:** Akt; EGFR; Hydrazone; Non-small cell lung cancer; STAT3; Thiazole. Copyright © 2026 Elsevier Inc. All rights reserved. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ## Similar articles * [ Design, synthesis and biological evaluation of a new series of imidazothiazole-hydrazone hybrids as dual EGFR and Akt inhibitors for NSCLC therapy. ](https://pubmed.ncbi.nlm.nih.gov/39047611/) Altıntop MD, Ertorun İ, Akalın Çiftçi G, Özdemir A.Altıntop MD, et al.Eur J Med Chem. 2024 Oct 5;276:116698. doi: 10.1016/j.ejmech.2024.116698. Epub 2024 Jul 20.Eur J Med Chem. 2024.PMID: 39047611 * [ Examining the 2-aryl-5-nitrobenzofuran-based hydrazones for anti-breast (MCF-7) cancer activity, potential to induce cell cycle arrest and inhibit receptor tyrosine kinases (VEGFR-2 & EGFR). ](https://pubmed.ncbi.nlm.nih.gov/40763666/) Nkoana JK, More GK, Elhenawy AA, Mphahlele MJ.Nkoana JK, et al.Eur J Med Chem. 2025 Nov 15;298:118018. doi: 10.1016/j.ejmech.2025.118018. Epub 2025 Aug 4.Eur J Med Chem. 2025.PMID: 40763666 * [ A new series of thiazole-hydrazone hybrids for Akt-targeted therapy of non-small cell lung cancer. ](https://pubmed.ncbi.nlm.nih.gov/36469421/) Orujova T, Ece A, Akalın Çiftçi G, Özdemir A, Altıntop MD.Orujova T, et al.Drug Dev Res. 2023 Apr;84(2):185-199. doi: 10.1002/ddr.22022. Epub 2022 Dec 5.Drug Dev Res. 2023.PMID: 36469421 * [ Design and synthesis of novel Thiazolo[5,4-b]pyridine derivatives as potent and selective EGFR-TK inhibitors targeting resistance Mutations in non-small cell lung cancer. ](https://pubmed.ncbi.nlm.nih.gov/39094428/) Borude AS, Deshmukh SR, Tiwari SV, Kumar SH, Thopate SR.Borude AS, et al.Eur J Med Chem. 2024 Oct 5;276:116727. doi: 10.1016/j.ejmech.2024.116727. Epub 2024 Jul 30.Eur J Med Chem. 2024.PMID: 39094428 * [ Small molecule allosteric modulators of mutant EGFR for non-small cell lung cancer therapy: An insight into design strategies and structure activity relationships. ](https://pubmed.ncbi.nlm.nih.gov/42501451/) Dash S, Ghosh M, Shehensha SK, Meduri R, Sahoo BM, Dhar AK, Dinda SC.Dash S, et al.Eur J Med Chem. 2026 Nov 15;318:119178. doi: 10.1016/j.ejmech.2026.119178. Epub 2026 Jul 21.Eur J Med Chem. 2026.PMID: 42501451Review. 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