Akademik Veri Yönetim Sistemi
EFMC-ASMC International Symposium on Advances in Synthetic and Medicinal Chemistry, Porto, Portekiz, 31 Ağustos - 04 Eylül 2025, ss.368, (Özet Bildiri)
Non-small cell lung cancer (NSCLC), which accounts for approximately 85% of all lung cancer cases, poses a
major threat to public health. One main impediment for the treatment of NSCLC is that most patients are
diagnosed at advanced or metastatic stages (stage III/IV) when the prognosis is poor and therapeutic options are
limited.
Epidermal growth factor receptor (EGFR) is overexpressed in many solid tumors, particularly in NSCLC. The
non-physiological activation of EGFR results in uncontrolled cell division and eventually tumor growth,
migration, stromal invasion, resistance to apoptosis, and angiogenesis. For this reason, EGFR is considered as a
promising target for the treatment of many cancer types, particularly NSCLC [1].
Akt, which has a central role in the phosphatidylinositol 3-kinase (PI3K)-Akt signaling network, is involved in
the pathogenesis of many types of cancer, including NSCLC, and therefore Akt inhibition by natural and
synthetic agents has come into prominence as a rational approach for cancer treatment and prevention [2].
Signal transducer and activator of transcription 3 (STAT3) is persistently activated in more than 50% of NSCLC
patients. STAT3 activation is associated with poor prognosis and tumor progression. Abnormal activation of
STAT3 plays a role in mediating chemoresistance in NSCLC, and overexpression of STAT3 is associated with
cisplatin resistance in NSCLC cells. STAT3 inhibition has also been reported to be an effective strategy to
overcome resistance to PI3K/Akt/mTOR inhibition. There are also numerous studies emphasizing the
therapeutic benefit of targeting STAT3 in NSCLC patients who are insensitive to current EGFR inhibitors.
Due to the importance of the thiazole scaffold for anticancer drug discovery [2], new thiazole-hydrazone hybrids
(1-20) were synthesized. The structures of compounds 1-20 were elucidated by Nuclear Magnetic Resonance
(NMR, 1H and 13C), and High Resolution Mass Spectrometry (HRMS). MTT assay was performed to investigate
their cytotoxic effects on A549 human lung adenocarcinoma cells and L929 mouse embryonic fibroblast cell
lines. Compounds 2, 5, 6, 7, 11, 14, 15, 18, 19 and 20 were determined as selective anticancer agents. In vitro
mechanistic studies were carried out to evaluate their effects on apoptosis, cell cycle, EGFR, Akt and STAT3.
2-[2-((6-Bromo-1,3-benzodioxol-5-yl)methylene)hydrazinyl]-4-(4-bromophenyl)thiazole (6) exerted marked
cytotoxic and apoptotic effects on A549 cells through the inhibition of EGFR, Akt and STAT3.