Modification of 7-piperazinylquinolone antibacterials to promising anticancer lead compounds: Synthesis and in vitro studies

Abstract

Amongst the fluoroquinolone antibacterials, the 7-piperazinyl containing chemotypes such as norfloxacin, enoxacin, ciprofloxacin, pefloxacin, lomefloxacin, enrofloxacin, ofloxacin, levofloxacin, gatifloxacin and sparfloxacin have been shown to possess non-classical activities including cytotoxicity against different cancer cell lines, induction of apoptosis, and cell cycle arrest at the S/G2 stage. Additionally, piperazinylquinolones (PQs) have enough flexibility for chemical modification via their N-4 of piperazine ring and carboxylic acid at C-3. Therefore, PQs have been considered as a starting point for design and development of new anticancer agents. This review has focused on the recent synthetic modifications of PQs which led to N-substituted and/or C-3 modified PQs with potential anticancer activity.

Keywords: 7-Piperazinylquinolones; Anticancer agents; Lead optimization; SAR study; Synthesis.