Anti-MRSA

The first time we encountered the Sugasawa reaction was in the early 1990s, when we worked on anti-MRSA carbapenem projects. We were very interested in this... 

Bush K, Heep M, Macielag MJ, Noel GJ. (2007) Anti-MRSA p-lactams in development, with a focus on ceftobiprole The first anti-MRSA p-lactam to demonstrate clinical efficacy. Expert Opin Invest Drugs 16 419 29. 

Kato A, Nakaya S, Ohashi Y, Hirata H. (1997) WAP-8294A2, a novel anti-MRSA antibiotic produced by Lysobacter sp. J Am Chem Soc 119 6680-6681. 

Among the many other non-oxicam-type substances discovered are a sultam pro-drug for potential P3-lactam thrombin inhibitors <1998BML3683>. Furthermore, an anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) pharmacophore based on the 1,2-thiazine structure has also been recently disclosed <1999BML673>. Workers at Bristol-Meyers Squibb have synthesized and evaluated sultam hydroxamates as MMP-2 inhibitors <2004JME2981>. Hydroxamate 38 displayed the best selectivity for MMP-2 over the other proteins in this superfamily of peptidases (Figure 27). As noted in Section 8.07.3.1, an X-ray crystal structure of 38 bound to the protein MMP-13 protein has been solved. 

We also screened anti-MRSA flavonoids [115] in the course of the study of anti-Helicobacter pylori flavonoids from licorice described in Chapter X. In our screening (Table 6), glabrene (24), licoisoflavone B (67), and gancaonin I (126) also exhibited anti-MRSA effect. Among these compounds, 23, 24, 27, 59, 61, 62, 63, 67, and 126 exhibited relatively high anti-bacterial activities against B. subtilis (HI7), Table 7. 

Nieuwlandt, D., Kellogg, E., Wecker, M., Qui, J., Wolk, S., Tarasow, T., Dewey, T., Eaton, B. Anti-MRSA drug leads from evolutionary chemistry. American Society of Microbiology (ASM) Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). 12-17 (2001). 

Table 15 Anti-MRSA Activity of Pterocarpans from the Genus Erythrina...

Compound Anti-MRSA range Ml( n MIC of resistant strains... 

Eriotrichin B 70 (also called Bidwillon A) was found 10 be antibacterial against S aureus with MIC50 of 8.3 pg/ml [20], while 2,3-dihydropratcnscin (5 7,3 -trihydroxy-4 -methoxyisoflavanone) 71 showed antifungal activity against Cladosporium cucumerinum (2 pg) in a TLC bioautography preliminary assay [12]. Orientanol F 72 showed Anti-MRSA... 

Yamazaki H, Koyama N, Omnra S, Tomoda H (2010) New Rugulosins, Anti-MRSA Antibiotics, Produced by Penicillium radicum FKI-3765-2. Org Lett 12 1572... 

Hardej et al. [22] have synthesized a series of rhodanine derivatives containing various substituents at the N3- and Cg-positions and tested for in vitro antibacterial activity against a panel of clinically relevant methicillin-resistant Staphylococcus aureus (MRSA) strains. The anti-MRSA activity of compounds II (minimum inhibitory concentration (MIC)=3.9 pg/mL) and in (MIC=1.95 pg/mL) were significantly greater than that of the reference antibiotics penicillin G (MIC=31.25 pg/mL) and ciprofloxacin (MIC=7.8 pg/mL). 

Strohal R, Schelling M, Takacs M, Jurecka W, Gruber U and Offner F, Nanocrystalline silver dressings as an efficient anti-MRSA barrier a new solution to an increasing problem . The Journal of Hospital Infection, 60 (3), 2005, pp 226-230. 

Activated sulfonamides and other activated amines were used in a series of Mitsunobu reactions to prepare analogs of 2-(sulfanamido)methyl carbapenems (124) as potential anti-MRSA compounds. The basic reaction scheme and some of the activated amines that were used are shown in the figure below. Additional examples can be found in the original paper. 

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