Abstract—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.


Index Terms— Colorectal cancer, EGFR, tyrosine kinase inhibitors, thiazolyl-pyrazoline.


Ayat Fayez is with Basic and Applied Sciences Institute, Egypt-Japan University of Science and Technology (E-JUST), New Borg El Arab, Alexandria, Egypt.
Sherif F. Hammad is with Basic and Applied Sciences Institute, Egypt-Japan University of Science and Technology (E-JUST), New Borg El Arab, Alexandria, Egypt and Pharmaceutical Chemistry Department, Faculty of Pharmacy, Helwan University, Ain Helwan, Cairo, Egypt.
Doaa A. Ghareeb is with Center of Excellence for Drug Preclinical Studies (CE-DPS), Pharmaceutical and Fermentation Industry Development Center, City of Scientific Research & Technological Applications, New Borg El Arab, Alexandria, Egypt. He is also with Bio-screening and Preclinical Trial Lab, Biochemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt and Biochemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt.
Maha Adel El Demellawy is with Center of Excellence for Drug Preclinical Studies (CE-DPS), Pharmaceutical and Fermentation Industry Development Center, City of Scientific Research & Technological Applications, New Borg El Arab, Alexandria, Egypt. He is also with Medical Biotechnology Department, Genetic Engineering and Biotechnology Research Institute, City of Scientific Research & Technological Applications, New Borg El Arab, Alexandria, Egypt.
Ahmed Osman is with Basic and Applied Sciences Institute, Egypt-Japan University of Science and Technology (E-JUST), New Borg El Arab, Alexandria, Egypt and Biochemistry Department, Faculty of Science, Ain shams University, Cairo, Egypt.

Cite: Ayat Fayez, Sherif F. Hammad, Doaa A. Ghareeb, Maha Adel El Demellawy, Ahmed Osman, " Novel Thiazolyl-Pyrazoline Analogs: Potential Role for Tyrosine Kinase Inhibition in Colorectal Cancer," International Journal of Bioscience, Biochemistry and Bioinformatics vol. 12, no. 2, pp. 22-29, 2022.

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