Antibacterial activity study

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Alves NM, Mano JF. (2008], Chitosan derivatives obtained by chemical modifications for biomedical and environmental applications. IntJ Biol Macromol, 43,401-414. 

Anal AK, Stevens WF. [2005]. Chitosan-alginate multilayer beads for controlled release of ampicillin. IntJ Pharm, 290,45-54. 

Ariel W. [2009]. Controlled Synthesis of Stimuli-responsive Network Alginate. PhD thesis. Queen s University, Canada. 

Bajpai SK, Ihnkhiwale R. [2006]. Investigation of water uptake behavior and stability of calcium alginate/chitosan bi-polymeric beads Part-1. React Fund Polym, 66,645-658. 

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Cephamydns, A family of fJ-lactam antibiotics produced by various Streptomyces species. Detection and production Stapley et at.. Antimicrvb. Ag. Chemother. 2, 122 (1972). Chemical characterization Miller et al, ibid. 132. Cephamycins A, B, and C have been isolated, tha latter being identical to a Streptomyces clavullgerus metabolite Nagarajan et ah. J. Am. Chem. Soc. 93, 2308 (1971). Structures Albers -Sehoenberg et ah, Tetrahedron Letters 1972, 2911- Antibacterial activity studies Miller et ah, dmimi-crob. Ag. Chemother. 2, 281, 287 (1972) Daoust et al. ibid. 3, 254 (1973). Review of syntheses T. Hiraoka et ah. Heterocycles 8, 719 (1977). 

In another attempt to relate degree of ionization with antibacterial activity, the effect of pH of the medium on the antibacterial activity was studied (27,28). Activity increased with increase in pH only up to the point at which the dmg was 50% ionized, and then decreased. The interpretation of this was that sulfonamides penetrate the bacterial cell in the unionized form, but once inside the cell, the equiUbrium between ionized and unionized forms is reestabhshed, and the activity is due to the ionized form. For optimum activity, a sulfonamide should have a p that provides half-dissociation at the physiologic pH in the area where it is absorbed. This observation also provided an explanation of the paraboHc relationship between piC and MIC (24). 

In common with the naturally occurring carbapenem thienamycin (2), the introduction of the /n j -6-[l-(R)-hydroxyethyi] group had a profound effect on the biological properties of the penems. This, together with an indication from an early study (93) that, as with other P-lactams, the 5(R)-enantiomer was solely responsible for antibacterial activity, provided impetus for the development of methods for the synthesis of chiral penems. 

All of the naturally-occurring monobactams discovered as of this writing have exhibited poor antibacterial activity. However, as in the case of the penicillins and cephalosporins, alteration of the C-3 amide side chain led to many potent new compounds (12). Furthermore, the monobactam nucleus provides a unique opportunity to study the effect of stmctural modifications at the N-1 and C-4 positions of the a2etidinone ring on biological activity. In contrast to the bicycHc P-lactams, these positions on the monocyclic ring system are readily accessible by synthesis. 

X-ray crystallographic studies (59) have defined the conformations and hydrogen bonding of the tetracyclines under nonpolar and polar conditions. These are shown ia Figure 3. It is beheved that the equiUbrium between the 2witterionic and nonioni2ed forms is of importance for the broad-spectmm antibacterial activity, membrane permeation, and pharmacokinetic properties. 

Studies on the mechanism of action of /3-lactam antibiotics have shed considerable light on how these agents kill bacteria. They also help explain qualitative differences between various agents and why there is a correlation between the reactivity of the /3-lactam and antibacterial activity. However, it is also clear that reactivity is only one factor in determining how effectively a given /3-lactam antibiotic will inactivate bacterial enzymes (82BJ(203)223). 

Modification at the C(7) position of the penam ring system (other than ring opening reactions) has not been extensively studied. It was possible, however, to convert the /3-lactam to a /3-thionolactam in 1% yield as shown in Scheme 55 (75JA5628). The deblocking product (73) had greatly reduced antibacterial activity compared to the parent /3-lactam. 

The thiophene analog of chloramphenicol (255) has been synthesized,as also have been similar structures. The antibacterial activity of all was much lower than that of the natural antibiotic. The thioamide of 2-thenoic acid has been prepared in a study of potential antitubercular compounds. It did not surpass thioisonico-tinamide in antitubercular activity. The thiosemicarbazones of thio-phenealdehydes and ketones (cf. Section VII,D) show high activity against Mycobacterium tuberculosis, but are very toxic. The thiosemi-carbazone of 4-(2-thienyl)-3-buten-2-one has been reported to be capable of completely inhibiting the in vitro growth of M. tuberculosis even in relatively low concentrations. ... 

S,3S)-Dicarboxyaziridine (112) was isolated from a Streptomyces strain in 1975 and found to have moderate antibacterial activity against Aeromonas salmonecida [176]. Subsequent studies showed that 112 acts as a competitive inhibitor of fumar-ase, through mimicry of a carbanionic transition state [177]. No biosynthetic studies have been reported for 112, but it is conceivable that it may arise from cydiza-tion of (3R)-hydroxyaspartic acid (Figure 11.18). 

The proteins of the outer membrane, many of which traverse the whole structure, are currently the subject of active study. Some of the proteins consist of three subunits, and these units with a central space or pore running through them are known as porrns. They are thought to act as a mechanism of selectivity for the ingress or exclusion of metabolites and antibacterial agents (see Chapter 8). 

The antibacterial activity of the obtained 3H-pyrazoles 63a,b and 64 has been studied. They have been tested opposite a pathogenic bacterial stump and have shown antibacterial activity against the original Staphyloccocusaureus. The 3H-pyrazole 63b offers the strongest antibacterial activity [56]. 

Similar to catechins, several studies have reported that proanthocyanidins exhibit a more or less pronoimced antibacterial activity. Chimg et al. [76] reported that proanthocyanidins determine the growth inhibition of strains of Aeromonas spp.. Bacillus spp., Clostridium botulinum, Clostridium per-fringens, Enterobacter spp., Klebsiella spp., Proteus spp.. Pseudomonas spp.. Shigella spp., S. aureus. Streptococcus spp., and Vibrio spp. 

Studies focused on the determination of SAR have revealed that the different enantiomeric form of catechins apparently affects their antibacterial activity. Bais et al. [101] found that (-i-)-catechin inhibited soil-borne bacteria of the species Xanthomonas campestris, R fluorescens, and Erwinia caro-... 

Studies on the antibacterial activities of mulberry phytoalexin in vitro it was 101... 

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. 

In 1975, SAR studies involving actinonin investigated an analogue in which the orientation of the Pl -P2 amide bond was reversed (13), but the compound was found to lack antibacterial activity. Since then, however, descriptions of some /i-aminohydroxamic acids and /i-amino-A-formyl-A-hydroxylamines as PDF inhibitors have appeared in the patent literature. Patent applications from Senju [97] and De Novo [98] pharmaceuticals cover Pl -P2 amides (14), ureas (15, 16) and sulfonamides (17). 

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