Intramolecular transformation of an antifungal antibiotic nystatin A₁ into its isomer, iso‐nystatin A₁ – structural and molecular modeling studies

Abstract

Nystatin A , a polyene macrolide antifungal antibiotic, in a slightly basic or acidic solution undergoes an intramolecular transformation, yielding a structural isomer, the translactonization product, iso-nystatin A with lactone ring diminished by two carbon atoms. Structural evidence is provided by advanced NMR and Mass Spectrometry (MS) studies. Molecular dynamics simulations and quantum mechanics calculations gave the insight into the course and mechanism of the transformation and its effect on the conformation of the subject molecule. Copyright © 2016 John Wiley & Sons, Ltd.

Molecular Umbrellas Modulate the Selective Toxicity of Polyene Macrolide Antifungals

“…The thus obtained preparations of NYS conjugates 14a – f contained tiny amounts (less than 4% by HPLC analysis, exemplary analysis of 14c preparation in Supporting Information) of respective isomeric forms (additional peak in HPLC, hardly distinguishable by preparative TLC, identified by HRMS and NMR analysis). These isomers were the products of the previously described intramolecular translactonization of NYS, resulting in formation of iso-nystatin (iso-NYS) . For the purpose of physicochemical and biological studies, each preparation was further purified by semipreparative HPLC, so that all results presented below were obtained for pure NYS conjugates, free of the iso-NYS derivatives.…”

“…These isomers were the products of the previously described intramolecular translactonization of NYS, resulting in formation of iso-nystatin (iso-NYS). 14 For the purpose of physicochemical and biological studies, each preparation was further purified by semipreparative HPLC, so that all results presented below were obtained for pure NYS conjugates, free of the iso-NYS derivatives.…”

Chitosan-Based Therapeutic Systems for Superficial Candidiasis Treatment. Synergetic Activity of Nystatin and Propolis

“…The structure of nystatin (NYS), its 13 C NMR and 1 H NMR spectra are given in Supplementary Materials, Figures S2 and S3, proving the high purity of the polyene macrolide [44][45][46]. The structure of chitosan and a comparison between the FTIR spectra of pristine chitosan powder and of the film prepared by its dissolving in aqueous lactic acid solution and drying are presented in Supplementary Materials, Figures S4 and S5, respectively.…”

“…The following supporting information can be downloaded at: https: //www.mdpi.com/article/10.3390/polym14040689/s1, Figure S1: Nystatin powder: (a) Scanning electron microscopy images for nystatin; (b) particle size distribution histogram (particle sizes were determined using NIH Image J software); Figure S2: 13 C-RMN spectrum of nystatin; IUPAC Name: (1S,3R,4R,7R,9R,11R,15S,16R,17R,18S,19E,21E,25E,27E,29E,31E,33R,35S,36R,37S)-33-[(2R,3S,4S,5S,6R)-4-amino-3,5-dihydroxy-6-methyloxan-2-yl]oxy-1,3,4,7,9,11,17,37-octahydroxy-15,16,18-trimethyl-13oxo-14,39-dioxabicyclo [3 3.3.1] nonatriaconta-19,21,25,27,29,31-hexaene-36-carboxylic acid); signal attributions made according to ref. [44][45][46]; Figure S3: 1 H-RMN spectrum of nystatin. IUPAC Name: 1S,3R,4R,7R,9R,11R,15S,16R,17R,18S,19E,21E,25E,27E,29E,31E,33R,35S,36R,37S)-33-[(2R,3S, 4S,5S,6R)-4-amino-3,5-dihydroxy-6-methyloxan-2-yl]oxy-1,3,4,7,9,11,17,37-octahydroxy-15,16,18-trimethyl-13oxo-14,39-dioxabicyclo[33.3.1]nonatriaconta-19,21,25,27,29,31-hexaene-36-carboxylic acid); signal attributions made according to ref.…”

“…IUPAC Name: 1S,3R,4R,7R,9R,11R,15S,16R,17R,18S,19E,21E,25E,27E,29E,31E,33R,35S,36R,37S)-33-[(2R,3S, 4S,5S,6R)-4-amino-3,5-dihydroxy-6-methyloxan-2-yl]oxy-1,3,4,7,9,11,17,37-octahydroxy-15,16,18-trimethyl-13oxo-14,39-dioxabicyclo[33.3.1]nonatriaconta-19,21,25,27,29,31-hexaene-36-carboxylic acid); signal attributions made according to ref. [44][45][46]; Figure S4: Chemical formula of chitosan with highlighting the functional groups: free primary amino groups (NH 2 to C2), primary hydroxyl group (OH to C6) and secondary hydroxyl groups (OH to C3); m and n represent the numbers of deacetylated (d-glucosamine) and N-acetyl-d-glucosamine repeating units, linked by (1-4)-β-glycosidic linkages, respectively; Figure S5: FTIR spectra of chitosan powder (CS) and chitosan gel (3%) after dispersion in 2% lactic acid solution (CS-LA); Figure S6: Characteristic stress-strain curves of the films: (a) without biological active compounds (CS-LA); (b) nystatin, propolis, and nystatin/propolis loaded chitosan films (CS-NYS, CS-PRO, CS-NYS-PRO1, CS-NYS-PRO2); Table S1: Parameters of pseudo-second order (PSO) and Korsmeyer-Peppas (K-P) kinetic models, where k s is the constant of the swelling rate, S e is the theoretical swelling capacity at equilibrium, k p is a constant dependent on the polymeric network; n is the diffusion parameter of aqueous PBS in the formulation film and SD represents the standard deviation of n = 11); swelling capacity in PBS of chitosan charged films after 5 and 24 h; Figure S7: Evolution in time of UV-VIS spectra of: nystatin released from CS-NYS (a), CS-NYS-PRO1 (b) and CS-NYS-PRO2 (c); propolis released from CS-PRO (d); Table S2: NYS and PRO release from chitosan films: Korsmeyer-Peppas kinetics parameters (k represents the transport constant, n is the diffusion exponent and SD is standard deviation of n = 11), and release efficiency after 5 and 24 h.; Figure S8. Sorption/desorption isotherms for the hydrogel formulations; Table S3.…”