1252678-95-7Relevant articles and documents
Development of novel antibacterial agents against methicillin-resistant Staphylococcus aureus
Chiu, Hao-Chieh,Lee, Su-Lin,Kapuriya, Naval,Wang, Dasheng,Chen, Yi-Ru,Yu, Sung-Liang,Kulp, Samuel K.,Teng, Lee-Jene,Chen, Ching-Shih
scheme or table, p. 4653 - 4660 (2012/08/29)
Methicillin-resistant Staphylococcus aureus (MRSA) poses a serious threat to public health because of its resistance to multiple antibiotics most commonly used to treat infection. In this study, we report the unique ability of the cyclooxygenase-2 (COX-2) inhibitor celecoxib to kill Staphylococcus aureus and MRSA with modest potency. We hypothesize that the anti-Staphylococcus activity of celecoxib could be pharmacologically exploited to develop novel anti-MRSA agents with a distinct mechanism. Examination of an in-house, celecoxib-based focused compound library in conjunction with structural modifications led to the identification of compound 46 as the lead agent with high antibacterial potency against a panel of Staphylococcus pathogens and different strains of MRSA. Moreover, this killing effect is bacteria-specific, as human cancer cells are resistant to 46. In addition, a single intraperitoneal administration of compound 46 at 30 mg/kg improved the survival of MRSA-infected C57BL/6 mice. In light of its high potency in eradicating MRSA in vitro and its in vivo activity, compound 46 and its analogues warrant continued preclinical development as a potential therapeutic intervention against MRSA.
