A Highly Potent Antibacterial Agent Targeting Methicillin-Resistant Staphylococcus aureus Based on Cobalt Bis(1,2-Dicarbollide) Alkoxy Derivative

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is a notorious superbug that is potentially lifethreatening. Among conventional antibiotics, vancomycin is a "gold standard" agent used to treat serious MRSA infections. Such therapy, however, is often ineffective because of the emergence of less-susceptible strains. Therefore, the exploration of new antimicrobial agents, especially nonantibiotic drugs, to cope with the growing threat of MRSA has become an urgent necessity. Herein, we have investigated the possibility to develop a metallacarborane antimicrobial agent, cobalt bis(1,2-dicarbollide) alkoxy derivative (K121), and we have evaluated the relevant anti-MRSA behaviors. We demonstrated that K121 has a dose-dependent anti-MRSA activity with a low minimal inhibitory concentration of 8 μg/mL and a high selectivity over mammalian cells. In particular, a high bacteria-killing efficiency was observed with eradication of all MRSA cells within 30 min. In addition, K121 showed a high inhibition effect on the formation of bacterial biofilm. More importantly, unlike vancomycin, a repeated use of K121 would not induce drug resistance even after 20 passages of MRSA. The mechanistic study showed that K121 kills MRSA by inducing an increase in the reactive oxygen species (ROS) production and consequentially inducing irreversible damage to the cell wall/ membrane, which ultimately leads to the death of MRSA. Our results suggested that K121 may be used as a promising nonantibiotic therapeutic agent against MRSA infections in future clinical practices.

Synthesis and study ofC-substituted methylthio derivatives of cobalt bis(dicarbollide)

“…[1][2][3][4][5] Among the various derivatives of carboranes, special attention is paid to p-complexes of transition metals with carborane ligands, called metallacarboranes. The most known of them, cobalt bis(dicarbollide) [3,3 0 -Co(1,2-C 2 B 9 H 11 ) 2 ] À attracts increasing interest from researchers working in various elds from medical chemistry to [6][7][8][9][10][11] materials science [12][13][14][15][16][17][18] to due to its extraordinary high stability, low toxicity 19 and almost unlimited possibilities for chemical modication. 20,21 Recently, we suggested that cobalt bis(dicarbollide) can be used as a structural element in the design of molecular switches.…”

Antimicrobial Gold Nanoclusters: Recent Developments and Future Perspectives

“…Furthermore, AuDAMP also can fight mutli-drug resistant bacteria such as E. coli , Acinetobacter baumannii (A. baumannii) , Pseudomonas aeruginosa , Klebsiella pneumonia (K. pneumonia) , methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (E. faecium). To kill bacteria, the mechanisms of antimicrobial AuDAMP have been demonstrated by the combination of cell membrane destruction, DNA damage and ROS generation caused by AuDAMP to bacteria (Figure 5) [95,96,97].…”

Periphery Decorated and Core Initiated Neutral and Polyanionic Borane Large Molecules: Forthcoming and Promising Properties for Medicinal Applications

“…The isomers of the closo-C2B10H12: ortho-(1,2), meta-(1,7), or para- (1,12); as well as nido-[C2B9H12]isomers: ortho-(7,8) and meta-(7,9). to obtain the hexaanion [1,2,8,9,10,12{3,3 [111] Li [112] Na [108] Na3 [109] Thiam. Significantly lower MICs versus wide-spectrum antibiotic thiamphenicol (used as positive control) are presented as follows: *P < 0.05, **P < 0.01, ***P < 0.001 vs. thiamphenicol Table 5.…”

“…[111] Recently, it has been reported that [3,3'-Co(8-CH3CH2O)2-1,2-C2B9H10)(1',2'-C2B9H11)]has a high bacteria-killing efficiency observed with eradication of all TSA MRSA cells within 30 min. [112] More importantly, unlike the vancomycin antibiotic, a repeated treatment with [3,3'-Co(8-…”