Supplementary Information - Masami OTSUKA; Mikako FUJITA; Belgin SEVER; Halilibrahim CIFTCI (2024)
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.
Keywords: cc-by-nc-4.0; Naphthalene; Pyrazoline; Thiazole; EGFR; NSCLC; Breast cancer