Amphiphilic aminoglycosides: Modifications that revive old natural product antibiotics

Abstract

Widely-used Streptomyces-derived antibacterial aminoglycosides have encountered challenges because of antibiotic resistance and toxicity. Today, they are largely relegated to medicinal topical applications. However, chemical modification to amphiphilic aminoglycosides can revive their efficacy against bacterial pathogens and expand their targets to other pathogenic microbes and disorders associated with hyperactive connexin hemichannels. For example, amphiphilic versions of neomycin and neamine are not subject to resistance and have expanded antibacterial spectra, and amphiphilic kanamycins are effective antifungals and have promising therapeutic uses as connexin hemichannel inhibitors. With further research and discoveries aimed at improved formulations and delivery, amphiphilic aminoglycosides may achieve new horizons in pharmacopeia and agriculture for Streptomyces aminoglycosides beyond just serving as topical antibacterials.

Evaluation of Poly(vinyl alcohol)–Xanthan Gum Hydrogels Loaded with Neomycin Sulfate as Systems for Drug Delivery

“…Neomycin is a natural hydrophilic aminoglycoside isolated mainly from Streptomyces sp. It is known for its bacteriostatic and bactericidal activity against Gram-positive and Gram-negative bacteria [ 51 ].…”

Quality by design‐engineered reversed‐phase high‐performance liquid chromatography method development and validation for simultaneous estimation of neomycin sulfate and beclomethasone dipropionate in bulk and pharmaceutical dosage form

“…It is commonly used to treat bacterial infections, particularly those caused by gram‐negative bacteria [4]. The medication is typically administered orally or applied topically, and in some cases, it may be used intravenously in severe infections [5]. Beclomethasone dipropionate (BECLO), Figure 1B, is a synthetic corticosteroid commonly used in the treatment of various inflammatory and allergic conditions [6].…”

Restoring susceptibility to aminoglycosides: identifying small molecule inhibitors of enzymatic inactivation

“…However, the development of resistance together with the aminoglycosides' relatively high toxicity, led to the development of semisynthetic molecules that are less toxic or refractory to one or more resistance mechanisms (see the representative referenced articles and reviews for a more extensive description). [23][24][25][26][27][28][29][30][31][32][33][34][35][36] Examples of aminoglycoside structures are shown in Fig. 1.…”