The anticancer therapeutic potential of pyrimidine-sulfonamide hybrids.

Cancer as a devastating malignancy, seriously threatens human life and health, but most chemotherapeutics have long been criticized for unsatisfactory therapeutic efficacy due to drug resistance and severe off-target toxicity. Pyrimidines, including fused pyrimidines, are privileged scaffolds for various biological cancer targets and are the most important class of metalloenzyme carbonic anhydrase inhibitors. Pyrimidine-sulfonamide hybrids can act on different targets in cancer cells simultaneously and possess potent activity against various cancers, revealing that hybridization of pyrimidine with sulfonamide is a promising approach to generate novel effective anticancer candidates. This review aims to summarize the recent progress of pyrimidine-sulfonamide hybrids with anticancer potential, covering papers published from 2020 to present, to facilitate further rational design of more effective candidates.