Synthesis and antibacterial activity study of a novel class of cationic anthraquinone analogs.
Reported previously by our group, one-pot cycloaddition using naphthoquinone, sodium azide and alkyl halides can lead to the formation of both 1-alkyl-1H- and 2-alkyl-2H-naphtho[2,3-d]triazole-4,9-diones. Herein, the effect of leaving group and additive in dictating the selectivity between the formation of 1-alkyl-1H- and 2-alkyl-2H-naphtho[2,3-d]triazole-4,9-diones has been further investigated. In the process of investigating the factors that control the selectivity and the biological activity associated with these two compounds, a novel class of antibacterial cationic anthraquinone analogs has been developed. Although these compounds are structurally similar, different antibacterial profiles are noted. One lead compound, 4e manifests high potency (MIC<1μg/mL) and selectivity against Gram positive (G+) pathogens including methicillin-resistant Staphylococcus aureus (MRSA) while exerting only modest activity against Gram negative (G-) bacteria. Other lead compounds (4f and 4g) exhibit broad antibacterial activity including MRSA and vancomycin-resistant Enterococcus faecalis (VRE) that is comparable to other commercially available cationic antiseptic chemicals. This unique difference in antibacterial profile may pave the way for the development of new therapeutic agents.
Department of Chemistry and Biochemistry, Utah State University, 0300 Old Main Hill, Logan, UT 84322-0300, USA.
Jianjun
J
Zhang
Nathan
N
Redman
Anthony Phillip
AP
Litke
Jia
J
Zeng
Jixun
J
Zhan
Ka Yee
KY
Chan
Cheng-Wei Tom
CW
Chang
D000880:Anthraquinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002412:Cations; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D021241:Spectrometry, Mass, Electrospray Ionization
D000880:Anthraquinones; D000900:Anti-Bacterial Agents; D002412:Cations