Advances in Medicinal Chemistry of Fused and Substituted Piperazines: Unlocking their Potential as Anticancer Agents

Abstract: Cancer is an abnormal growth of normal cells and has become a global healthcare concern. The availability of safer anticancer drugs with exceptional selectivity for healthy cells and high efficacy against various forms of cancer remains a significant challenge. Therefore, there is a need to develop target-specific and safer anticancer drugs. In medicinal chemistry, heterocyclic compounds play a crucial role by exhibiting diverse biological activities. Specifically, nitrogen-containing heterocyclic compounds are widely studied due to their diverse activities. The piperazine moiety serves as the building block for several molecules and is reported to have the ability to inhibit the cell cycle (G1/S phase), suppress angiogenesis, and interact with DNA. Piperazine also exhibits a flexible binding feature that enables it to interact with a range of biological targets, making it effective against various types of cancer. As there is a continuous need for an anticancer drug with improved efficacy and fewer side effects, piperazine derivatives are attracting the attention of researchers. This review highlights recent methods for the synthesis of fused and substituted piperazines, their structure–activity relationships, and their interactions with biological targets or receptors as anticancer agents. Thus, the presented review will be helpful to medicinal chemists in designing anticancer molecules that incorporate piperazines.