Anticancer potential and structure activity studies of purine and pyrimidine derivatives: an updated review

Abstract

Cancer is the world's leading cause of death impacting millions of lives globally. The increasing research over the past several decades has focused on the development of new anticancer drugs, but still cancer continues to be a global health challenge. Thus, several new alternative therapeutic strategies have been tried for the drug design and discovery. Purine and pyrimidine heterocyclic compounds have received attention recently due to their potential in targeting various cancers. It is evident from the recently published data over the last decade that incorporation of the purine and pyrimidine rings in the synthesized derivatives resulted in the development of potent anticancer molecules. This review presents synthetic strategies encompassing several examples of recently developed purine and pyrimidine-containing compounds as anticancer agents. In addition, their structure-activity relationships are represented in the schemes indicating the fragment or groups that are essential for the enhanced anticancer activities. Purine and pyrimidines combined with other heterocyclic compounds have resulted in many novel anticancer molecules that address the challenges of drug resistance. The purine and pyrimidine derivatives showed significantly enhanced anticancer activities against targeted receptor proteins with numerous compounds with an IC₅₀ value in the nanomolar range. The review will support medicinal chemists and contribute in progression and development of synthesis of more potent chemotherapeutic drug candidates to mitigate the burden of this dreadful disease.

Keywords: Cancer; Heterocyclic compounds; Nucleobases; Purine; Pyrimidine.