Antibacterial activity, reviews

Mechanism of Antibacterial Action. In spite of the fact that the antibacterial activity of the amiaoglycosides has been known siace the 1940s, the mechanisms iavolved are stiU incompletely understood. Numerous reviews have appeared (eg, 108 —113) and the sequence of events seems to be as outlined below. 

Clavulanic acid has only weak antibacterial activity, but is a potent irreversible inhibitor for many clinically important P-lactamases (10—14,57,58) including penases, and Richmond-Sykes types 11, 111, IV, V, VI ([Bacteroides). Type I Cephases are poorly inhibited. Clavulanic acid synergizes the activity of many penicillins and cephalosporins against resistant strains. The chemistry (59—63), microbiology (64,65), stmcture activity relationships (10,13,60—62,66), biosynthesis (67—69), and mechanism of action (6,26,27,67) have been reviewed. 

As can be seen from Table 3, only modifications at the 6/3-amino groups have been successful in producing penicillins of medical significance up to this time. Several reviews have dealt with the structure-activity relationship in this area in considerable detail B-80MI51102, B-77MI51106, B-75MI51102) and should be consulted for the actual effects of structural modification on antibacterial activity. 

Gillis JC, Brogden RN Rifaximin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic potential in conditions mediated by gastrointestinal bacteria. Drugs 1995 49 467-484. 

Jiang ZD, DuPont HL Rifaximin In vitro and in vivo antibacterial activity. A review. Chemotherapy 2005 51(suppl 1) 67—72. 

The coordination shell comprises three fac-S and three fac-N-donor atoms in [Fe(6mp)3] [FeClJCl, where 6mp = 6-thiopurine, (189). Both iron(II) and iron(III) complexes are included in a review of transition metal complexes of thiosemicarbazones. " 5,5 -Dimethyl-l,2,3-cyclohex-anetrione-l,2-dioxime-3-thiosemi-carbazone, dcdt (190), acts as an A, A, 5 -donor to Fe +, giving a bis-ligand complex (contrast [Fe(7V,7V -dcdt)3] with Fe " "). The Schiff bases from pyridine 2-carboxaldehyde and thiosemicarbazide or 4-phenyl thiosemicarbazide also act as A, VV, 5 -donors, both to Fe " " and to Fe " ". The antibacterial activity of these complexes was assessed, in... 

Of commercial interest are benzo- and other fused aromatic 1,2,3-diazaborine derivatives which have exhibited good antibacterial activity against a variety of microorganisms (155—157). The reaction of pyrazole or C-substituted pyrazoles with boranes yields the pyrazabole system, a class of exceptionally stable compounds. More than 70 species in this system have been reported and the subject comprehensively reviewed (158). These compounds have been used as ligands in transition-metal complexes (159). 

Patents have been granted for innovations involving the preparation and activities of broad-spectrum antimicrobial emulsions from 1977 (Sippos) to 2000 (Baker). All of these patents claim antibacterial activity, but all involve additives in the non-aqueous phase of the emulsion that are known to be antibacterial alone and before emulsification. Wide spectrum applications for these nanoemulsions have been claimed with positive results for bacteria, fungi, and viruses. The term nanoemulsion is used in US patents discussed below, but the generic term for the product of an emulsification (Gooch 2002, 1980) of a liquid within a liquid is an emulsion. United States patents 6,015,832 and 5,547,677 were examined and formulations in key claim statements were reproduced, and tested using standard methods for effectiveness. Additional patents listed in the reference section were reviewed as part of this study. 

A QSAR seeks to relate quantitative properties (descriptors) of a compound with other properties such as drug-like activity or toxicity. The essential assumption of QSAR is that quantities that can be conveniently measured or calculated for a compound can be used to accurately predict another property of interest (e.g., antibacterial activity) in a nontrivial way. QSAR has become an integral part of screening programs in pharmaceutical drug-discovery pipelines of small compounds and more recently in toxicological studies (69). However, the use of QSAR modeling applied to the search for antimicrobial peptides is relatively recent. Advances in this area are reviewed in brief here. 

---