Novel Thiazolyl-Pyrazoline Analogs: Potential Role for Tyrosine Kinase Inhibition in Colorectal Cancer

: Colorectal cancer (CRC) ranked the third and the second in the onset and mortality rates, respectively, among all types of cancer (GLOBOCAN 2020). In this study, we targeted epidermal growth factor receptor (EGFR) using two synthesized thiazolyl pyrazoline analogs in presence and absence of berberine as an adjuvant remedy. Preliminary results showed that these compounds exert anti-neoplastic and tyrosine kinase inhibitory effects against lung cancer cell lines. We assessed the anticancer activities of these compounds via quantitative determination of transcripts levels (qRT-PCR) of some apoptotic and proliferative markers in Caco-2 cell line. Our data showed a synergistic augmented effect between the tested compounds and berberine on the pro-apoptotic markers (BAX and p53). Furthermore, the oncogenes EGFR and c-MYC, as well as the anti-apoptotic gene ARC, exhibited downregulation trend. In conclusion, the novel compounds show promising results as potential TKI that inhibit malignant cell growth and restore cancer cells' apoptotic capacity. strategy to hinder the signaling pathways associated with EGFR by binding to its ATP binding sites. We aimed to investigate the potential of novel thiazolyl pyrazolines to inhibit EGFR expression and apoptosis induction when added with the natural isoquinoline berberine. Our results showed a good synergism where P53 was upregulated with its downstream transcription targets BAX and Fas, indicating apoptosis activation. Furthermore, EGFR and TGF-b were downregulated post-treatment suggesting a decline in cell proliferation and migration. Overall, we recommend combining berberine and thiazolyl pyrazoline derivatives to enhance colorectal cancer treatment.