The College of Pharmacy discussed the PhD dissertation entitled “Insilico Study, Synthesis, and Preliminary Cytotoxicity Evaluation of New 4H-1,4-Benzothiazine Derivatives” by the student Haider Jabbar Madloul and his supervisor, Assistant Professor Dr. Mohammed Kamil Hadi, at the Pharmaceutical Chemistry Department.
The study aimed to study new 4H-1,4-benzothiazine derivatives of ethyl 4H-benzo[b] [1,4] thiazine-3-carboxylate, which synthesized by the reaction of 2-amino-thiophenol with ethyl bromopyruvate in a slightly basic medium. From this ester, a 4H-benzo[b][1,4]thiazine-3-carbohydrazide was synthesized. Three different series of derivatives were successfully synthesized; 6 Schiff bases derivatives, 4 sulphonamides derivatives, and 3 semicarbazides derivatives
The study included Insilco study of a new 4H-1, 4-benzothiazine derivatives, characterization spectroscopically and invitro cytotoxicity evaluation of them against two cell line
The study concluded that in-vitro cytotoxicity assay (MTT assay) demonstrated that all target compounds possess high cytotoxicity effects (IC50 less than 20 µM). Therefore the most promise derivatives against both 4HJO and MCF-7 cancer cell lines were SH6, S4, and CN1.
The results showed that the most cytotoxic derivate against A549 lung cancer cell line were SH6 possesses (IC50: 3.88µM), S4 possesses (IC50:4.18 µM), and CN1 possesses (IC50: 7.58 µM) compared with reference Erlotinib possesses (IC50: 3.86µM); Also all synthesized compounds are promise as anti- proliferative against MCF7 cancer cell line but the most cytotoxic derivate were SH6 possesses (IC50: 2.71µM), S4 possesses (IC50: 2.68 µM), and CN3 possesses (IC50: 3.50 µM).
The study recommended to complete the pharmacokinetic studies of all synthesized compounds, further invitro cytotoxic activity research on different cancer cell lines and invivo study is recommended, study the selectivity of the target compounds against EGFR and evaluation of the synthesized compounds against other targeted receptors like FGFR.
