New naphthalene-linked pyrazoline-thiazole hybrids as prominent antilung and antibreast cancer inhibitors.

The epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2), pioneer members of the receptor tyrosine kinase subfamily, are frequently mutated and/or overexpressed in several types of human cancers, including nonsmall cell lung cancer (NSCLC) and breast cancer, which are leading causes of cancer-related deaths worldwide. EGFR and HER2-focused anti-NSCLC and antibreast cancer studies encouraged us to search for new potential agents. For this purpose, in the current work, naphthalene-linked pyrazoline-thiazole hybrids (BTT-1-10 and BTP-1-10) were synthesized and examined for their antiproliferative effects on A549 NSCLC and MCF-7 breast cancer cell lines. According to the results, the MTT assay showed that BTT-5 induced strong toxicity in A549 cells with an 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 the 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, showing its selective kinase inhibitory effects. The 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.