Piperazine thiourea derivatives against clinical strains of colistin-resistant Acinetobacter baumannii. Synthesis and in vitro biological evaluation

Acinetobacter baumannii is a typical nosocomial pathogen that is now recognized as a mayor problem in healthcare because its high mortality rate. In the last years, antimicrobial resistance of different species of Acinetobacter has increased substantially and it is resistant to many classes of antibiotics. Colistin is nowadays, one of the last therapeutic options to treat these infections. However, colistin resistant strains are being isolated with higher frequency. Currently, there are no antibiotics commercially available to treat these resistant infections [1]. Based on our previous work [2], we report the synthesis of 4 acyl-1-phenylaminocarbonyl-2-substitued piperazine derivatives, following a short and high yielded methodology, and in vitro evaluation of antimicrobial activity against clinical isolated of colistin-resistant A. baumannii strains. We have identified four active compounds that showed growth inhibition (MIC 3.12 μM) against 46% of the A. baumannii assayed strains and without cytotoxicity. Further studies will need to better identify the specific target for these new molecules and optimize their antibacterial activity.