Staphylococcus aureus inhibitor

Tricyclic pyrazole derivatives (698) are described by Hashem et al. as inhibitors of the growth of Bacillus subtilis, Pseudomonas fluorescens, Staphylococcus aureus and KB cells at moderate concentrations (76JMC229). 

Deformylation of nascent polypeptides has been shown to be a function essential for growth in E. coli, Staphylococcus aureus and Streptococcus pneumoniae [15-18]. Moreover, antibacterial mode of action studies, using S. pneumoniae or S. aureus strains in which the expression of PDF is controlled by regulatable promoters, have shown that the antibacterial activity of PDF inhibitors is due to their inhibition of the PDF enzyme, as the susceptibility of the strains to these compounds is dependent on the amount of protein present in the cell [19-21]. These results further validate PDF as a target for novel antibiotics. 

Pereda-Miranda R, Kaatz GW, Gibbons S (2006) Polyacylated Oligosaccharides from Medicinal Mexican Morning Glory Species as Antibacterials and Inhibitors of Multidrug Resistance in Staphylococcus aureus. J Nat Prod 69 406... 

Tincture of the dried seed, on agar plate at a concentration of 30 p,L/disc, was inactive on Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. Extract of 10 g plant material in 100 mL ethanol was used b Anticoagulation activity. Serpin BSZx (an inhibitor of trypsin and chemotrypsin) inhibited thrombin, plasma kallikrein, factor Vlla/tissue factor, and factor Xa at heparin-independent association rates. Only factor Xa turned a significant fraction of BSZx over as substrate. Activated protein C and leukocyte elastase were slowly inhibited by BSZx, whereas factor Xlla, urokinase and tissue type plasminogen activator, plasmin and pancreas kallikrein, and elastase were not or only weakly affected. Trypsin from Fusarium was not inhibited, while interaction with subtilisin Carlsberg and Novo was rapid, but most BSZx was cleaved as a substrate L... 

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. 

The researchers custom-designed a screening assay to search for a FabF inhibitor in the extracts. They engineered a strain of Staphylococcus aureus to produce antisense RNA that gives them tight control of the amount of FabF produced. ... 

Vermisporin (41) is produced by the fungus Ophiobolus vermisporis [76]. Its structure was determined by chemical degradation to the derivative (42) which was studied by X-ray crystallography and provided the absolute configuration [77]. Vermisporin exhibits antimicrobial activity towards Bacteroides spp (0.25-2 lg/ml), Clostridium perfringens (0.25-2 pg/ml) and methicillin-resistant Staphylococcus aureus (0.12-0.5 pg/ml). A metabolite of Ophiobolus rubellus produces the tetramic acid (43) that has been claimed to be an inhibitor of proline hydroxylase (IC5019pM) [78]. 

Staphylococcus aureus - [ANTIBIOTICS - BETA-LACTAMS - CEPHALOSPORINS] (Vol 3) - [DISINFECTANTS AND ANTISEPTICS] (Vol 8) - [ANTIBIOTICS - BETA-LACTAMS - BETA-LACTAMASE INHIBITORS] (Vol 3) - [ANTIBIOTICS - LINCOSAMINIDES] (Vol3) - [ANTIBIOTICS - BETA-LACTAMS - PENICILLINS AND OTHERS] (Vol 3) - [ANTIBIOTICS-AMINOGLYCOSIDES] (Vol2) - [ANTIBIOTICS - GLYCOPEPTIDES(DALBAHEPTIDES)] (Vol 2) -bacitracin resistance [ANTIBIOTICS - PEPTIDES] (Vol 3) -ethanol activity against [DISINFECTANTS AND ANTISEPTICS] (Vol 8) -inhibited by sorbates [SORBIC ACID] (Vol 22)... 

Decatromicins A (1218) and B (1219) are produced by an Actinomadura sp. and are active against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (1229,1230). These compounds are closely related to pyrrolosporin A (1220) from Micromonospora sp. (1231,1232). The ascidian Polycitor africanus from Madagascar has afforded the new polycitone B (1221) (1233), which is related to the known polycitone A (1), a potent inhibitor of retroviral reverse transcriptases and cellular DNA polymerases (1234). The known polycitrin B was synthesized for the first time (1235). 

A new halogen-containing member of the penitrem family of indole-diterpe-noids, which have insecticidal activity (1397), is thomitrem A (1466) from Penicil-lium crustosum (1398). The novel dichlorinated calmodulin inhibitor, malbrancheamide (1467), was characterized from the fungus Malbranchea auran-tiaca (1399). The microbe Streptomyces rugosporus produces pyrroindomycin B (1468), which is active against both methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci (1400). The Chinese shrub Acacia confusa has yielded the unusual chlorotryptamine alkaloid 1469, which does not appear to be an artifactual dichloromethane adduct (1401). 

Serai, C., et al. 2003. Influence of P-glycoprotein and MRP efflux pump inhibitors on the intracellular activity of azithromycin and ciprofloxacin in macrophages infected by Listeria monocytogenes or Staphylococcus aureus. J Antimicrob Chemother 51 1167. 

Staphylococcus aureus Abscesses bacteremia cellulitis endocarditis osteomyelitis pneumonia others If methicillin-sensitive nafcillin or oxacillin If methicillin-resistant vancomycin gentamicin or rifampin 1 st-generation cephalosporin clindamycin erythromycin trimethoprim-sulfamethoxazole a penicillin + a penicillinase inhibitor... 

M- Sponei, H. Nick, and H. P. Schnebli. Different susceptibility of elastase inhibitors to inactivation by proteioases from Staphylococcus aureus and Pseudomonas aeruginosa. Biol Chan. Hoppe-Seyler 372 963 (1991). 

Bottcher T, Sieber SA (2008) P-Lactones as specific inhibitors of ClpP attenuate the production of extracellular virulence factors of Staphylococcus aureus. J Am Chem Soc 130 14400-14401... 

Phenyl-l,2,3-triazolo[4,5-d]pyrimidin-7(6//)-one has bactericidal activity against Bacillus subtilis and Staphylococcus aureus (94MI2). 1-Benzyl-4-ethoxycarbonylpiperazinyl-l//-l,2,3-triazolo[4,5-d]pyrimidine almost completely removed cytokinin-stimulated effects in betacyanin synthesis in Amaranthus caudatus cotyledons, growth of radish cotyledons, and retention of chlorophyll in leaf explants (94MI4). Analogs of 117 were used as effective inhibitors of xanthine oxidase (95FA257). 

Jarvest, R.L. et al. 2002. Nanomolar inhibitors of Staphylococcus aureus methionyl tRNA synthetase with potent antibacterial activity against gram-positive pathogens. J. Med. Chem. 45, 1959-1962. 

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