Various Novel Erythromycin Derivatives Obtained by Different Modifications: Recent Advance in Macrolide Antibiotics

Abstract

The rapid emergence of drug resistance intensified the search for new antimicrobial agents, leading to lots of novel derivatives obtained from 14- and 15-membered macrolides by chemical modifications. Many of them exhibited enhanced antibacterial activity and expanded antibacterial spectrum. Especially some of them were found to be potent for the treatment of multi-drug-resistant bacterial infections. Besides, the other biological effects of macrolide derivatives were also found. In this article, we reviewed the recent advance in the novel macrolide derivatives designed by different structural modifications on erythronolide skeleton, cladinose and desosamine in the structures.

Actinomycete-Derived Polyketides as a Source of Antibiotics and Lead Structures for the Development of New Antimicrobial Drugs

“…This accumulation causes depletion of the free tRNA pool, whereby protein biosynthesis is inhibited [65]. In order to improve the chemical, microbiological, and pharmacokinetic properties of macrolides, a lot of effort was put into the production of semi-synthetic and synthetic derivatives [63,170,171]. Some of the most successful semi-synthetic derivatives produced from erythromycin include the 14-membered clarithromycin and roxithromycin and the nitrogen-containing 15-membered azithromycin ( Figure 2) [73,74].…”

“…Some of the most successful semi-synthetic derivatives produced from erythromycin include the 14-membered clarithromycin and roxithromycin and the nitrogen-containing 15-membered azithromycin ( Figure 2) [73,74]. Clarithromycin (trade name: Biaxin, Table 1) and roxithromycin (not commercially available, Table 1) were discovered in the 1980s in screening programs aiming at identification of erythromycin A variants with improved acidic stability and [166][167][168][169] In order to improve the chemical, microbiological, and pharmacokinetic properties of macrolides, a lot of effort was put into the production of semi-synthetic and synthetic derivatives [63,170,171]. Some of the most successful semi-synthetic derivatives produced from erythromycin include the 14-membered clarithromycin and roxithromycin and the nitrogen-containing 15-membered azithromycin ( Figure 2) [73,74].…”

Macrolide Antibiotics

“…A lot of research has been directed at improving the bioavailability and pharmacokinetic and pharmacodynamic properties of the macrolides (Zuckerman et al, 2009;Ma and Ma, 2010), through structural modifications, and this field remains of great interest (Liang et al, 2010;Sugimoto and Tanikawa, 2011).…”

Precursor Directed Biosynthesis of an Orthogonally Functional Erythromycin Analogue: Selectivity in the Ribosome Macrolide Binding Pocket

“…The polyketides are a large class of natural products with clinically important activities ranging from anticancer (doxorubicin) to immunosuppression (FK-506) and, perhaps most prominently, antibacterial. A prototypical polyketide, erythromycin A ( 1a ), is produced by the soil bacterium Saccharopolyspora erythraea and has been in clinical use as a macrolide antibiotic for more than half a century. , Its medicinal chemistry has been extensively explored with an eye toward improving its therapeutic potential. , While these efforts have yielded significant advances, such as the discovery of the second-generation macrolides, clarithromycin and azithromycin, as well as the third-generation ketolide, telithromycin, the intrinsic structural complexity of 1a has greatly hindered more fundamental variations in the core structure to obtain agents of improved potency and antibacterial spectrum.…”