Chemistry and biology of the polyene macrolide antibiotics

Hamilton‐Miller, J. M. T.

doi:10.1128/br.37.2.166-196.1973

Cited by 95 publications

(32 citation statements)

References 162 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Identity of CndD, ParA, ParB, isoCndD, isoParA and isoParB was confirmed by 1 H NMR, 2D 1 H DQF-COSY (Double Quantum Filtered-Correlation Spectroscopy) NMR, mass spectrometry (MS) and UV-Vis spectroscopy. UV-Vis spectra and MS data are presented in HPLC chromatograms (Figure S1A-F), complete 1 H NMR spectra are presented as Figure S2A-F and the most informative fragments of DQF-COSY spectra are presented as Figure S3A-F. All these data, particularly molecular peaks in MS spectrum with m/z values equal to M + 1 of each compound, differences in relative intensities of the longest wavelength absorption peaks, their batochromic shift~6 nm in UV-Vis spectra, and characteristic patterns of signals in DQF-COSY spectra, confirmed that isoCndD, isoParA and isoParB are all-trans isomers of CndD, ParA and ParB, respectively.…”

Section: Preparation and Confirmation Of Identity Of Candicidin D Partricin A Partricin B And Their All-trans Isomersmentioning

confidence: 99%

“…demonstrate antifungal activity. They are characterized by a large macrocyclic lactone ring (macronolide) containing a system of 3-7 conjugated double bonds and a number of hydrophilic substituents, including a glycosidically bound aminosugar, most often D-mycosamine (3,6-dideoxy-3amino-D-mannose) [1]. The most interesting and prospective group of polyene macrolides are the heptaenes, with Amphotericin B (AmB) still being considered as 'the lifesaving drug' and 'the golden standard' for antifungal agents [2].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Quest for the Molecular Basis of Improved Selective Toxicity of All-Trans Isomers of Aromatic Heptaene Macrolide Antifungal Antibiotics

Borzyszkowska-Bukowska

Górska

Szczeblewski

et al. 2021

IJMS

View full text Add to dashboard Cite

Three aromatic heptaene macrolide antifungal antibiotics, Candicidin D, Partricin A (Gedamycin) and Partricin B (Vacidin) were subjected to controlled cis-trans ® all trans photochemical isomerization. The obtained all-trans isomers demonstrated substantially improved in vitro selective toxicity in the Candida albicans cells: human erythrocytes model. This effect was mainly due to the diminished hemotoxicity. The molecular modeling studies on interactions between original antibiotics and their photoisomers with ergosterol and cholesterol revealed some difference in free energy profiles of formation of binary antibiotic/sterol complexes in respective membrane environments. Moreover, different geometries of heptaene: sterol complexes and variations in polyene macrolide molecule alignment in cholesterol-and ergosterol-containing membranes were found. None of these effects are of the crucial importance for the observed improvement of selective toxicity of aromatic heptaene antifungals but each seems to provide a partial contribution.

show abstract

Section: Preparation and Confirmation Of Identity Of Candicidin D Partricin A Partricin B And Their All-trans Isomersmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Quest for the Molecular Basis of Improved Selective Toxicity of All-Trans Isomers of Aromatic Heptaene Macrolide Antifungal Antibiotics

Borzyszkowska-Bukowska

Górska

Szczeblewski

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…Resistance to polyenes is usually produced by increasing the synthesis of other sterols, leading to the emergence of fungal species with reduced ergosterol content in the cell membrane [72]. Other mechanisms reported include enhanced catalase activity, replacement, reorientation, and/or masking of some or all the polyene-binding sterols with those sterols with lower affinity to polyenes [73,74]. Resistance to the azole group of drugs occurs through multiple mechanisms and is more complex than that of the polyene group.…”

Section: Challenges In Azole-and Polyene-based Therapymentioning

confidence: 99%

Recent Perspectives in the Management of Fungal Keratitis

Raj

Vanathi

Ahmed

et al. 2021

JoF

View full text Add to dashboard Cite

Mycotic keratitis is common in warm, humid regions with a varying profile of pathogenic fungi according to geographical origin, socioeconomic status, and climatic condition. Clinical diagnosis can be challenging in difficult cases and those refractory to treatment. Fungal hyphae on microscopic examination and culture isolation have been the gold standard in the laboratory diagnosis of fungal keratitis. A culture isolate of the aetiological fungus is essential to perform antifungal susceptibility testing. As the culture isolation of fungi is time-consuming, causing delays in the initiation of treatment, newer investigative modalities such as in vivo confocal microscopy and molecular diagnostic methods have recently gained popularity. Molecular diagnostic techniques now help to obtain a rapid diagnosis of fungal keratitis. Genomic approaches are based on detecting amplicons of ribosomal RNA genes, with internal transcribed spacers being increasingly adopted. Metagenomic deep sequencing allows for rapid and accurate diagnosis without the need to wait for the fungus to grow. This is also helpful in identifying new emerging strains of fungi causing mycotic keratitis. A custom-tear proteomic approach will probably play an important diagnostic role in future in the management of mycotic keratitis. Positive repeat cultures are being suggested as an important gauge indicative of a poor prognosis. Positive repeat fungal cultures help to modify a treatment regimen by increasing its frequency, providing the addition of another topical and oral antifungal agent along with close follow-up for perforation and identifying need for early therapeutic keratoplasty. The role of collagen crosslinking in the treatment of fungal keratitis is not convincingly established. Rapid detection by multiplex PCR and antifungal susceptibility testing of the pathogenic fungi, adopted into a routine management protocol of fungal keratitis, will help to improve treatment outcome. Early therapy is essential in minimizing damage to the corneal tissue, thereby providing a better outcome. The role of conventional therapy with polyenes, systemic and targeted therapy of antifungal agents, newer azoles and echinocandins in fungal keratitis has been widely studied in recent times. Combination therapy can be more efficacious in comparison to monotherapy. Given the diversity of fungal aetiology, the emergence of new corneal pathogenic fungi with varying drug susceptibilities, increasing the drug resistance to antifungal agents in some genera and species, it is perhaps time to adopt recent molecular methods for precise identification and incorporate antifungal susceptibility testing as a routine.

show abstract

“…NTM is a tetraene macrolide antibiotic that is produced by S. natalensis and exhibits antifungal activity [13,22]. Therefore, we hypothesized that strain NBRC14001 may produce compound(s) with antifungal activity.…”

Section: The Genome-guided Approach Revealed That Strain Nbrc14001 Produces Compound(s) That Exhibit Antifungal Activitymentioning

confidence: 99%

“…Based on this information, we herein revealed that S. achromogenes subsp. streptozoticus NBRC14001 produces lucensomycin (LCM), a tetraene macrolide antibiotic that exhibits antifungal activity [13]. LCM is an important antibiotic because it is useful for postharvest disease control against gray mold on grapes [14].…”

Section: Introductionmentioning

confidence: 99%

Genome Sequence-Guided Finding of Lucensomycin Production by Streptomyces achromogenes Subsp. streptozoticus NBRC14001

et al. 2021

View full text Add to dashboard Cite

Information on microbial genome sequences is a powerful resource for accessing natural products with significant activities. We herein report the unveiling of lucensomycin production by Streptomyces achromogenes subsp. streptozoticus NBRC14001 based on the genome sequence of the strain. The genome sequence of strain NBRC14001 revealed the presence of a type I polyketide synthase gene cluster with similarities to a biosynthetic gene cluster for natamycin, which is a polyene macrolide antibiotic that exhibits antifungal activity. Therefore, we investigated whether strain NBRC14001 produces antifungal compound(s) and revealed that an extract from the strain inhibited the growth of Candida albicans. A HPLC analysis of a purified compound exhibiting antifungal activity against C. albicans showed that the compound differed from natamycin. Based on HR-ESI-MS spectrometry and a PubChem database search, the compound was predicted to be lucensomycin, which is a tetraene macrolide antibiotic, and this prediction was supported by the results of a MS/MS analysis. Furthermore, the type I polyketide synthase gene cluster in strain NBRC14001 corresponded well to lucesomycin biosynthetic gene cluster (lcm) in S. cyanogenus, which was very recently reported. Therefore, we concluded that the antifungal compound produced by strain NBRC14001 is lucensomycin.

show abstract

Chemistry and biology of the polyene macrolide antibiotics

Cited by 95 publications

References 162 publications

Quest for the Molecular Basis of Improved Selective Toxicity of All-Trans Isomers of Aromatic Heptaene Macrolide Antifungal Antibiotics

Quest for the Molecular Basis of Improved Selective Toxicity of All-Trans Isomers of Aromatic Heptaene Macrolide Antifungal Antibiotics

Recent Perspectives in the Management of Fungal Keratitis

Genome Sequence-Guided Finding of Lucensomycin Production by Streptomyces achromogenes Subsp. streptozoticus NBRC14001

Contact Info

Product

Resources

About