Synthesis, in silico studies, and in vitro biological evaluation of newly-designed 5-amino-1H-tetrazole-linked 5-fluorouracil analog as a potential antigastric-cancer agent.

5-Fluorouracil (5FU) is a chemotherapy drug used to treat various cancers, such as colorectal, prostate, skin, pancreas, and stomach, as an ointment or solution. However, its consumption has several side effects. Therefore, a new derivative of fluorouracil containing 5-Amino-1H-tetrazole was designed and synthesized through multi-step synthesis to reduce urea excretion and toxicity. The effectiveness of the synthesized drug on the Adenocarcinoma gastric cell line (AGS) gastric cancer cell line was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test, which showed that the new 5-fluorouracil (5FU) analog, with an IC50 of 15.67 µg/mL, is more effective in inhibiting the proliferation of AGS cells after 24 h compared to both synthesized and reported 5FU. In addition, In-silico studies showed that the new 5FU derivative based on amino tetrazole, with a binding energy of -7.2 kcal/mol, exhibits greater anti-cancer activity against the BCL2 enzyme than 5FU, with a binding energy of - 4.8 kcal/mol. It is predicted that the new 5FU derivative will be effective in treating gastric and colorectal cancers. The new derivative of the 5-fluorouracil drug was characterized and identified using FTIR and NMR spectroscopy.Communicated by Ramaswamy H. Sarma.