Aminoglycoside antibiotics structural relationships

Reden, J., and Diirckheimer, W. Aminoglycoside Antibiotics — Chemistry, Biochemistry, Structure-Activity Relationships. 83, 105-170 (1979). 

Reviews by Hanessian et al. [20], Umezawa [21], and Cox et al. [22] deal with the chemistry of aminoglycosides Price [23] has reviewed structure-activity relationships, and Umezawa et al. [24,25] have discussed the structure, synthesis, and biosynthesis of aminoglycoside antibiotics. This chapter summarizes what is known of the stmctural classes of aminoglycosides to date and presents state-of-the-art knowledge of the mechaiusms for manifestation of the biological activities of these versatile antimicrobials. 

A-Glysyllysinomicin (415) and several 4-A-aminoacyl analogs of lysinomicin derivatives (compounds 416 18) have been prepared to examine the effect of 4-A-aminoacylation on antibacterial activity of this class of aminoglycoside antibiotics (compounds 414 18 ). In contrast to lysinomicin, which is slightly more potent than fortimicin A (372), the new analogs showed lower activity than the 4-A-unsubstituted lysinomicin derivatives, indicating that the structure-activity relationship observed with fortimicins does not apply to lysinomicin derivatives [248]. 

The discovery of Gentamydn and its successful utilisation for the treatment of serious gram-negative infections has contributed in the last years to increasing clinical use and to a rapid development of the chemistry and biochemistry of aminoglycoside antibiotics. Also of importance in the further exploration of this class of compounds are the new chemical and physico-chemical methods, e.g. H- and C-NMR-spectroscopy, mass spectroscopy. X-ray analysis and the different chromatographic methods. Synthetic efforts and studies of the inactivation mechanism have provided a preliminary insight into the relationship between structure and activity. 

Aminoglycoside Antibiotics - Chemistry, Biochemistry Structure-Activity Relationships... 

The classification of aminoglycoside antibiotics in this Chapter will be based on overall, common structural relationships, being divided into the seven groups discussed in Section II. 

The papers given at a symposium on aminocyclitol antibiotics have been published most are reports of the synthesis of naturally occurring compounds or their conversion to modified analogues in search of improved antibiotic activity. A review has also appeared covering the structure, physicochemical and biological properties, structure-activity relationships, and mode of action of aminoglycoside antibiotics. ... 

The structure-activity relationships among the aminoglycoside antibiotics, based on bacterial inhibition and misreading of polypeptide synthesis, was discussed.1 0... 

Many of the same chromatographic and spectroscopic techniques were applied to the isolation and identification of natural products such as carbohydrates and glyco-lipids. The discovery, isolation, computational analysis, synthesis, and structure-activity relationship studies of antibiotics such as the aminoglycosides kanamycin and neamine are of particular note (Fig. 1.14) [157, 158],... 

Tetracyclines were the first broad-spectrum antibiotics and have been used successfully for decades to treat both gram-positive and gram negative bacterial infections (82). Chlortetra-cycline was the first tetracycline to be isolated, in 1948, from Streptomyces aureofaciens (83). Other common tetracyclines, such as oxytet-racycline and tetracycline, were isolated from Streptomyces sources in subsequent years. The abundance of natural, active tetracyclines, coupled with extensive synthetic alterations, provides a rich collection of compounds from which to build meaningful structure-activity relationships. As was found for the aminoglycosides, previous observations of tetracycline structure and activity can be rationalized from recent tetracycline/30S crystal structures (11,12). 

---