Pyrimidine hybrids with in vivo anticancer therapeutic potential

Chemotherapy has transformed cancer from a catastrophic disease to a treatable and sometimes curable disease, but multidrug resistance is a predominant obstacle to effective chemotherapy, creating an urgent demand to explore novel anticancer therapeutics. Pyrimidine is necessary to maintain cellular fundamental function and is critical in cancer cell proliferation as well as survival, and some pyrimidine-based agents have been developed as anticancer therapeutics. In particular, pyrimidine hybrids can act on distinct biological targets in cancer cells simultaneously and have potential advantages in increasing anticancer therapeutic efficacy and circumventing drug resistance, indicating that the rational design of pyrimidine hybrids may provide valuable therapeutic interventions for cancer therapy. This review outlines the current scenario of the in vivo anticancer therapeutic potential of pyrimidine hybrids, together with pharmacokinetic properties, toxicity, and modes of action developed from 2020 onwards, aiming to provide potential candidates for further preclinical/clinical evaluations and facilitate the rational design of more candidates.