Synthesis and anticancer activity investigation of some novel benzoxazole derivatives

Cancer is a complicated disease which can ensue in different organs and systems of body. Deaths from cancer worldwide are awaited to reach 12 million in the year 2030. The reasons of increase in the patient population over the years are development of resistance to existing chemotherapeutics, non-selective anticancer drugs and toxic effects. Thus, there is still a need to develop new chemotherapeutic agents. Phortress including benzothiazole moiety is a prodrug displaying anticancer activity. The active metabolite of Phortress is a potent agonist of the aryl hydrocarbon receptor (Ahr) and switches on cytochrome P450 CYP1A1 gene expression. Besides, piperazine, a hydrophylic structure, is found in the structure of some anticancer drugs as imatinib and razoksan. In this study, some benzoxazole derivatives were synthesized to develop new anticancer agents. The benzothiazole ring in Phortress altered with its bioisoster benzoxazole. Piperazine was added to structure of compounds to increase polarity, transport through cell membrane and anticancer activity. Syntheses of compounds were performed according to literature methods. Their structures were elucidated by IR, 1H-NMR, 13C-NMR, 2D-NMR and HRMS spectroscopic methods. Anticancer activity tests were performed on colon (HT-29), breast (MCF7), lung (A549), liver (HepG2) and brain (C6) carcinoma cell types. Induction potential of the compounds 3m and 3n on CYP1A1/2 enzymes was investigated. Biotransformation studies for 3m and 3n was examined by LCMS-IT-TOF system. Docking studies for compound 3n and its some metabolites were performed. Keywords: Benzoxazole, Piperazine, Phortress, Anticancer, CYP1A1