Erythromycin structure-activity relationship

This chapter deals with recent progress in the chemical modification and structure-activity relationships of 14- and 15-membered macrolides (mainly erythromycin derivatives), 16-membered macrolides (mainly the leucomycin and tylosin families), and the avermectin family of macrolides, showing nematocidal, insecticidal, and arachnidicidal activities. Previous reviews of these macrolides were given by Sakakibara and Omura in the first edition of this book in 1984 [1]. 

Gasc, J.-C., D Ambrieres, S, G, Lutz, A., and Chantot, J. R (1991). New ether oxime derivatives of erythromycin A. A structure-activity relationship study. J. Antibiot. 44, 313-330. Morimoto, S., Takahashi, Y., Watanabe, Y, and Omura, S. (1984). Chemical modification of erythromycins. 1. Synthesis and antibacterial activity of 6-0-methylerythromycins A. J. Antibiot. 37, 187-189. 

Djokic, S., Kobrehel, G., and Lazarevski, G. (1987). Erythromycin series. XII. Antibacterial in vitro evaluation of 10-dihydro-10-deoxo-11-azaerythromycin A Synthesis and structure-activity relationship of its acyl derivatives. J. Antibiot. 40, 1006-1015. 

These studies on modifications to erythromycin A have provided a great deal of important and interesting pharmacokinetic improvements, broadening an antibacterial spectrum and developing potency. For details, see Weisblum [183] and Bryskier et al. [207, 208]. Further work on structure-activity relationships in macrolide antibiotics with due consideration for their water solubility will provide a sufficient opportunity to improve antibacterial macrolides. 

Antibiotics may be classified by chemical structure. Erythromycin, chloramphenicol, ampicillin, cefpodoxime proxetil, and doxycycline hydrochloride are antibiotics whose primary structures differ from each other (Fig. 19). Figure 20 shows potential oscillation across the octanol membrane in the presence of erythromycin at various concentrations [23]. Due to the low solubility of antibiotics in water, 1% ethanol was added to phase wl in all cases. Antibiotics were noted to shift iiB,sDS lo more positive values. Other potentials were virtually unaffected by the antibiotics. On oscillatory and induction periods, there were antibiotic effects but reproducibility was poor. Detailed study was then made of iiB,sDS- Figure 21 (a)-(d) shows potential oscillation in the presence of chloramphenicol, ampicillin, cefpodoxime proxetil, and doxycycline hydrochloride [21,23]. Fb.sds differed according to the antibiotic in phase wl and shifted to more positive values with concentration. No clear relationship between activity and oscillation mode due to complexity of the antibacterium mechanism could be discovered but at least it was shown possible to recognize or determine antibiotics based on potential oscillation measurement. 

---