•  
  •  
 

Turkish Journal of Chemistry

Abstract

Epidermal growth factor receptor (EGFR) and HER2, pioneer members of the receptor tyrosine kinase subfamily, are frequently mutated and/or overexpressed in several types of human cancers, including non-small cell lung cancer (NSCLC) and breast cancer, which are leading causes of cancer-related deaths worldwide. EGFR and HER2-focused anti-NSCLC and anti-breast cancer studies encouraged us to search for new potential agents. For this purpose, in the current work, naphthalene-linked pyrazoline-thiazole hybrids (BTT1-10 and BTP1-10) were synthesized and examined for their antiproliferative effects on A549 NSCLC and MCF-7 breast cancer cell lines. According to the results, MTT assay showed that BTT-5 induced strong toxicity in A549 cells with the IC50 value of 9.51±3.35 μM compared to lapatinib (IC50 = 16.44±3.92 μM). BTT-5 also presented a high selectivity profile between Jurkat cell line and PBMCs (healthy) (SI= 65.65). Furthermore, BTT-5 augmented apoptosis significantly in A549 cells (18.40%). BTT-5 displayed significant EGFR inhibition (58.32%) and no significant HER2 inhibition at 10 μM concentration interpreting its selective kinase inhibitory effects. Molecular docking assessment indicated that BTT-5 showed high affinity with a different binding profile than lapatinib in the ATP binding cleft of EGFR. Consequently, BTT-5 can serve as a lead for future anti-NSCLC studies.

Author ORCID Identifier

HALİLİBRAHİM ÇİFTÇİ: 0000-0002-9796-7669

MASAMI OTSUKA: 0000-0002-2968-3939

MIKAKO FUJITA: 0000-0001-6705-4052

BELGİN SEVER: 0000-0003-4847-9711

DOI

10.55730/1300-0527.3704

Keywords

Naphthalene, pyrazoline, thiazole, epidermal growth factor receptor, nonsmall cell lung cancer, breast cancer

First Page

856

Last Page

866

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Download

Included in

Chemistry Commons

Share

COinS