Design of Organoiron Dendrimers Containing Paracetamol for Enhanced Antibacterial Efficacy

摘要

Paracetamol (acetaminophen) is a common painkiller and antipyretic drug used globally. Attachment of paracetamol to a series of organoiron dendrimers was successfully synthesized. The aim of this study is to combine the benefits of the presence of these redox-active organoiron dendrimers, their antimicrobial activities against some human pathogenic Gram-positive, and the therapeutic characteristics of paracetamol. The antimicrobial activity of these dendrimers was investigated and tested with a minimum inhibitory concentration and this has been reported. Some of these newly synthesized dendrimers exhibited the highest inhibitory activity against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecium (VRE), and Staphylococcus warneri compared to reference drugs. The results of this study indicate that the antimicrobial efficacy of the dendrimers is dependent on the size of the redox-active organoiron dendrimer and its terminal functionalities. The best result has been recorded for the fourth-generation dendrimer 11, which attached to 48 paracetamol end groups and has 90 units composed of the η6-aryl-η5-cyclopentadienyliron (II) complex. This dendrimer presented inhibition of 50% of the growth (IC50) of 0.52 μM for MRSA, 1.02 μM for VRE, and 0.73 μM for Staphylococcus warneri. The structures of the dendrimers were characterized by elemental analysis, Fourier transform infrared (FT-IR), nuclear magnetic resonance (1H-NMR), and 13C-NMR spectroscopic techniques. In addition, all synthesized dendrimers displayed good thermal stability in the range of 300–350 °C following the degradation of the cationic iron moieties which occurred around 200 °C.