Activity Study of ۵-Fluorouracil Derivatives as an Anticancer (In Silico and In Vitro)

۵-Fluorouracil (۵-Fu) is an antimetabolite class of anticancer agents that induces apoptosis by inhibiting thymidylate acid biosynthesis. Drug Development of ۵-fluorouracil is an effort to obtain higher activity and a specific target receptor compared with ۵-fluorouracil as a first-line drug for breast cancer. ۵-Fluorouracil derivatives (۲-Cl-benzoyloxymethyl-۵Fu, ۳-NO۲-benzoyloxymethyl-۵Fu, ۴-OCH۳-benzoyloxymethyl-۵Fu, ۴-CF۳-benzoyloxymethyl-۵Fu, ۳,۴-Cl-benzoyloxymethyl-۵Fu, and ۴-NO۲-benzoyloxymethyl-۵Fu) were successfully synthesized and identified but have not been studied in silico and in vitro (cytotoxic activity, and immunocytochemistry (p۵۳, telomerase, and apoptosis) in MCF۷). The First step, in silico study, showed that ۵-Fu derivatives had better binding affinity than ۵-Fu. The second step was an in vitro study, which included cytotoxicity tests and immunocytochemistry. The cytotoxicity test showed that the best IC۵۰ was ۳-NO۲-benzoyloxymethyl-۵-Fu among other ۵-Fu derivatives with ۳۴۸,۳۹۸ µM. The results of immunocytochemistry telomerase, p۵۳, and apoptosis (double staining and flowcytometry) studies revealed that ۴-NO۲-benzoylooxymethyl-۵-Fu, ۴-CF۳-benzoylooxymethyl-۵-Fu, and ۴-methoxybenzoylooxymethyl-۵-Fu activity were better than other ۵-Fu derivatives and ۵-Fu as a lead compound. In general, the results showed that ۵-Fluorouracil derivatives had a significant effect (in vitro and in silico study) compared with ۵-Fluorouracil

کلیدواژه ها:

۵-fluorouracil ، activity study ، Anticancer ، ۵-Fu derivatives ، In Silico ، In vitro