Antibacterial Polyketides from the Marine Alga-Derived Endophitic Streptomyces sundarbansensis: A Study on Hydroxypyrone Tautomerism

Abstract

Polyketide 13 [=2-hydroxy-5-((6-hydroxy-4-oxo-4H-pyran-2-yl)methyl)-2-propylchroman-4-one] and three related known compounds 7, 9 and 11 were obtained and structurally characterized from Streptomyces sundarbansensis strain, an endophytic actinomycete isolated from the Algerian marine brown algae Fucus sp. Compound 13 was obtained as the major metabolite from optimized culture conditions, by using Agar state fermentation. Due to tautomeric equilibrium, 13 in CD3OD solution was able to incorporate five deuterium atoms, as deduced by NMR and ESI-MS/MS analysis. The 2-hydroxy-γ-pyrone form was established for these metabolites based on the comparison of their experimental IR spectra with the DFT calculated ones, for both the corresponding 4-hydroxy-α-pyrone and 2-hydroxy-γ-pyrone forms. During antibacterial evaluation, compound 13 stood out as the most active of the series, showing a selective activity against the gram positive pathogenic methicillin-resistant S. aureus (MRSA, MIC = 6 μΜ), with a bacteriostatic effect.

Metabolite profile of marine-derived endophytic Streptomyces sundarbansensis WR1L1S8 by liquid chromatography-mass spectrometry and evaluation of culture conditions on antibacterial activity and mycelial growth

“…In our previous work, polyketide 1 has shown the highest antibacterial activity, with a selective inhibition of methicillin resistance Staphylococcus aureues (MRSA) [MIC = 2 μg ml −1 , 6 μmol l −1 ] (Djinni et al . ), a promising result for further investigations.…”

“…By injection under the same conditions of compound 2, previously purified and structurally characterized (Djinni et al . ), it was possible to establish that the peak at t R = 3·72 min corresponded to phaeochromycin B. Similarly, the peak at t R = 10·6 min was assigned to compound 1.…”

“…Extensive NMR analysis and MS fragmentation experiments on the purified compounds resulted in the identification of the metabolites (Djinni et al . ), corresponding to the HPLC peaks, in detail 4 ( t R = 2·21 min), 2 ( t R = 3·72 min), 1 ( t R = 10·61 min) and 3 ( t R = 15·56 min).…”

“…All the metabolites are members of the phaeochromycins class, for which we have recently proposed the favoured 2‐hydroxy‐γ‐pyrone structure based on a comparison of experimental and calculated IR spectra (Djinni et al . ). They are analogues of the polyketides peculiar for the presence of a propyl side chain.…”

Nuclear Magnetic Resonance Spectroscopy for Structural Characterization of Bioactive Compounds

“…Thus changing CDCl 3 for CD 3 OD, the 1 H NMR spectrum of the antibacterial marine chroman-4-one 14 showed a fast disappearance of three signals corresponding to an olefinic proton, as a singlet at 5.33 ppm, and two methylene protons, as doublets at 2.79 and 2.89 ppm, due to tautomeric equilibria (Scheme 7.1). The incorporation of five deuterium atoms (the previously described plus the OD groups) was confirmed by ESI(+)-MS [14].…”