Synthesis and diverse biological activities of piperazine derivatives: a systematic review on their current status (2020–2025)

Piperazine is one of the most commonly employed nitrogen-containing heterocycles in the development of pharmacologically active molecules. The adaptable structure of piperazine has made it preferable in the synthesis of novel bioactive molecules for the last several years. However, there is a lack of comprehensive information about the current status of the synthesis and medicinal application of piperazine derivatives. Therefore, this systematic review aims to compile research articles reported in the past six years (between 2020 and 2025) dealing with the various synthetic methodologies and biological activities of piperazine derivatives. The papers compiled in this review were collected from major databases and search engines. Among the various reported piperazine derivatives, compounds 41b , 41d , 42f , and 43e with an MIC of 0.391 μg/mL against S. aureus ; compound 98a with an MIC of 0.65 μg/mL against M. tuberculosis ; compound 207f with an IC 50 value of 1.86 ± 0.03 μM against breast cancer cell line (MCF-7); and compound 218i against Zika virus (ZIKV) with an EC 50 of 0.82 ± 0.33 μM were mentioned as promising compounds for various medicinal applications. This review could be beneficial to researchers as a source of compiled and up-to-date preliminary information by highlighting the synthetic methodologies and various medicinal applications of the piperazine derivatives.