Medicinal chemistry aspects of uracil containing dUTPase inhibitors targeting colorectal cancer

Deoxyuridine-5-triphosphate nucleotidohydrolase (dUTPase), a vital enzyme in pyrimidine metabolism, is a prime target for treating colorectal cancer. Uracil shares structural traits with DNA/RNA bases, prompting exploration by medicinal chemists for pharmacological modifications. Some existing drugs, including thymidylate synthase (TS) and dUTPase inhibitors, incorporate uracil moieties. These derivatives hinder crucial cell proliferation pathways encompassing TS, dUTPases, dihydropyrimidine dehydrogenase, and uracil-DNA glycosylase. This review compiles uracil derivatives that have served as dUTPase inhibitors across various organisms, forming a library for targeting human dUTPase. Insights into their structural requisites for human applications and comparative analyses of binding pockets are provided for analyzing the compounds against human dUTPase.