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Conversion of Natural Products from Renewable Resources in Pharmaceuticals by Cytochromes P450
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Giovanna Di Nardo, Gianfranco Gilardi
Cytochromes P450 catalyzed reactions in some cases need to be avoided to provide molecules with higher biological activity and/or lower toxicity. This is the case of amphotericin B from Streptomyces nodosus, which acts by sequestering ergosterol, which is essential for fungal cell membranes (Hartsel and Bolard, 1996). Since this compound has shown some toxic effects due to the interaction with different targets, derivatives were produced and a QSAR analysis revealed the functional groups necessary for biological activity, specificity toward ergosterol versus cholesterol and showed that toxicity was decreased in those derivatives where the negative charge on the exocyclic carboxyl was reduced (Cheron et al., 1988). On this basis, a bacterial strain was engineered to have a gene amphN coding for a cytochrome P450 involved in the synthesis of amphotericin B deleted to produce amphotericin analogues where the exocyclic carboxyl groups were substituted by methyl group functionalities (Carmody et al., 2005). These analogs were shown to retain antifungal activity as well as lower toxicity compared to the starting compound.
Therapeutic Approach in Fungal Keratitis
Published in Mahendra Rai, Marcelo Luís Occhiutto, Mycotic Keratitis, 2019
Victoria Díaz-Tome, María Teresa-Rodríguez Ares, Rubén Varela-Fernández, Rosario Touriño-Peralba, Miguel González-Barcia, Laura Martínez-Pérez, María Jesús Lamas, Francisco J. Otero-Espinar, Anxo Fernández-Ferreiro
Amphotericin B was the first broad-spectrum antifungal agent discovered. It was isolated for the first time in 1950 from the Streptomyces nodosus actinobacteria (Caffrey et al. 2001). It has a broad spectrum of action against yeasts (Candida spp.) and filamentous fungi (Aspergillus spp., Penicillium spp.) (Ellis 2002).
History of antifungals
Published in Mahmoud A. Ghannoum, John R. Perfect, Antifungal Therapy, 2019
Emily L. Larkin, Ali Abdul Lattif Ali, Kim Swindell
Amphotericin B is a fungicidal polyene antibiotic and, like other members of the polyene class, is effective against organisms with sterol-containing cell membranes [19]. Amphotericin B was extracted from Streptomyces nodosus, a filamentous bacterium, at the Squibb Institute for Medical Research in 1955 and subsequently served as the standard treatment for many invasive fungal infections [33].
Fungal sphingolipids: role in the regulation of virulence and potential as targets for future antifungal therapies
Published in Expert Review of Anti-infective Therapy, 2020
Caroline Mota Fernandes, Maurizio Del Poeta
The polyenes are natural products of Streptomyces nodosus, a soil actinomycete [4], and amphotericin B, its main prototype, has been used for systemic fungal infections since 1959. Despite its clinical use for several decades, amphotericin B is still one of the most potent antifungals, exhibiting a broad spectrum of activity, including against most isolates of Cryptococcus spp, Candida spp and Aspergillus spp. For a long time, it was thought that amphotericin B exerts its fungicidal activity through the formation of pores. However, Gray showed that the antifungal activity of this polyene relies on simply binding to ergosterol, subsequently disrupting membrane function [5]. The membrane permeabilization caused by channel formation constitutes a secondary mechanism which increases amphotericin B potency [6].
The management of Babesia, amoeba and other zoonotic diseases provoked by protozoa
Published in Expert Opinion on Therapeutic Patents, 2023
Clemente Capasso, Claudiu T. Supuran
Amphotericin B deoxycholate (Fungizone) 27, was isolated from the actinomycete Streptomyces nodosus. This drug is a broad-spectrum macrocyclic polyene antibiotic with a high antileishmania effect, and its liposomal formulations have significant efficacy [128]. Fungizone binds to Leishmania plasma membrane ergosterol, forming aqueous holes in cell membranes and disrupting parasite metabolism, leaking small intracellular molecules, and killing cells [128]. Unfortunately, its use has been hampered by several difficulties, such as its instability at high temperatures, low oral bioavailability, nephrotoxic effects, hypokalemia and myocarditis [129,130].
Neonatal fluid and electrolytes profile effect on amphotericin B associated nephrotoxicity in neonatal tertiary care unit of Karachi-Pakistan
Published in Expert Opinion on Drug Safety, 2020
Gul Ambreen, Arshalooz Rehman, Kashif Hussain, Mehreen Sohail, Saba Javed, Syed Shamim, Umer Ali, Khalil Ahmad, Arjumand Rizvi
Conventional amphotericin B-deoxycholate (d-AmB) is a polyene macrolide isolated from Streptomyces nodosus, is commonly used to treat IFIs in adults and children [15,16]. d-AmB has a broader anti-fungal spectrum [17]. Due to the high prevalence and mortality rate of IFIs in neonates, d-AmB is used empirically and therapeutically in septic neonates. Prophylactic treatment with antifungals may influence the reliability of culture reports therefore at times d-AmB treatment is started based on highly raised serum levels of β-d-glucan (BDG) >80 pg/mL [18]. Empiric antifungal therapy is reported to reduce death and neurodevelopmental impairment in neonates [19].