Iso-Partricin, an Aromatic Analogue of Amphotericin B: How Shining Light on Old Drugs Might Help Create New Ones

Abstract

Partricin is a heptaene macrolide antibiotic complex that exhibits exceptional antifungal activity, yet poor selective toxicity, in the pathogen/host system. It consists of two compounds, namely partricin A and B, and both of these molecules incorporate two cis-type bonds within their heptaenic chromophores: 28Z and 30Z. In this contribution, we have proven that partricins are susceptible to a chromophore-straightening photoisomerization process. The occurring 28Z→28E and 30Z→30E switches are irreversible in given conditions, and they are the only structural changes observed during the experiment. The obtained all-trans partricin’s derivatives, namely iso-partricins A and B, exhibit very promising features, potentially resulting in the improvement of their selective toxicity.

Dancing with sterols: can antibiotic-sterol interactions explain the selectivity of aromatic analogues of amphotericin B?

“…The alkyl-aromatic moiety of aromatic polyene macrolides displayed three possible orientations in relation to the antibiotics' macrolide ring: aligned, bent and tucked up (Fig. [9][10][11][12]. Careful examination of the side chain's behavior in relation to the membranes themselves (Fig.…”

New Glycosylated Polyene Macrolides: Refining the Ore from Genome Mining

“…Heterologous expression of AceS N-methylase in Streptomyces albidoflavus did not result in the formation of methylated candicidins in vivo [43]. Controlled UV irradiation gives specific and irreversible conversion of aromatic heptaenes to all trans forms [44,45]. This reduces hemolytic activity and improves selective toxicity [46].…”

“…Otherwise, there is agreement between predicted and experimentally determined chirality and double-bond geometry. Controlled UV irradiation gives specific and irreversible conversion of aromatic heptaenes to all trans forms [44,45]. This reduces hemolytic activity and improves selective toxicity [46].…”

Effect of mobile phase pH on liquid chromatography retention of mepartricin related compounds and impurities as support to the structural investigation by liquid chromatography–mass spectrometry

“…Polyene macrolides are a versatile and promising family of fungicidal agents belonging to antifungal and anti-protozoal antibiotics [1]. Among them, partricin was first isolated from a strain of Streptomyces aureofaciens and showed to be very active against fungi and protozoa.…”

“…However, partricin has not therapeutic application to date since it shows a relatively poor pathogen/host selective toxicity and a significant hemolytic activity [2]. Nevertheless, recent studies suggest a significant decrease in toxicity because of double bonds trans to cis isomerization, suggesting potential future applications [1].…”