Activity Study of 5-Fluorouracil Derivatives as an Anticancer (In Silico and In Vitro)
نویسندگان
1 Biomedical Department, Faculty of Pharmacy, University of Jember, Jember, Indonesia.
2 Medicinal Chemistry Department, Faculty of Pharmacy, University of Jember, Jember, Indonesia.
3 Biomedical Department, Faculty of Pharmacy, University of Jember, Jember, Indonesia.
doi
10.22034/crl.2025.535201.1658چکیده
5-Fluorouracil (5-Fu) is an antimetabolite class of anticancer agents that induces apoptosis by inhibiting thymidylate acid biosynthesis. Drug Development of 5-fluorouracil is an effort to obtain higher activity and a specific target receptor compared with 5-fluorouracil as a first-line drug for breast cancer. 5-Fluorouracil derivatives (2-Cl-benzoyloxymethyl-5Fu, 3-NO2-benzoyloxymethyl-5Fu, 4-OCH3-benzoyloxymethyl-5Fu, 4-CF3-benzoyloxymethyl-5Fu, 3,4-Cl-benzoyloxymethyl-5Fu, and 4-NO2-benzoyloxymethyl-5Fu) were successfully synthesized and identified but have not been studied in silico and in vitro (cytotoxic activity, and immunocytochemistry (p53, telomerase, and apoptosis) in MCF7). The First step, in silico study, showed that 5-Fu derivatives had better binding affinity than 5-Fu. The second step was an in vitro study, which included cytotoxicity tests and immunocytochemistry. The cytotoxicity test showed that the best IC50 was 3-NO2-benzoyloxymethyl-5-Fu among other 5-Fu derivatives with 348,398 µM. The results of immunocytochemistry telomerase, p53, and apoptosis (double staining and flowcytometry) studies revealed that 4-NO2-benzoylooxymethyl-5-Fu, 4-CF3-benzoylooxymethyl-5-Fu, and 4-methoxybenzoylooxymethyl-5-Fu activity were better than other 5-Fu derivatives and 5-Fu as a lead compound. In general, the results showed that 5-Fluorouracil derivatives had a significant effect (in vitro and in silico study) compared with 5-Fluorouracil