New Napyradiomycin Analogues from Streptomyces sp. Strain CA-271078

Abstract

As part of our continuing efforts to discover new bioactive compounds from microbial sources, a reinvestigation of extracts of scaled-up cultures of the marine-derived Streptomyces sp. strain CA-271078 resulted in the isolation and structural elucidation of four new napyradiomycins (1–3, 5). The known napyradiomycin SC (4), whose structural details had not been previously described in detail, and another ten related known compounds (6–15). The structures of the new napyradiomycins were characterized by HRMS and 1D- and 2D-NMR spectroscopies and their relative configurations were established through a combination of molecular modelling with nOe and coupling constants NMR analysis. The absolute configuration of each compound is also proposed based on biosynthetic arguments and the comparison of specific rotation data with those of related compounds. Among the new compounds, 1 was determined to be the first non-halogenated member of napyradiomycin A series containing a functionalized prenyl side chain, while 2–4 harbor in their structures the characteristic chloro-cyclohexane ring of the napyradiomycin B series. Remarkably, compound 5 displays an unprecedented 14-membered cyclic ether ring between the prenyl side chain and the chromophore, thus representing the first member of a new class of napyradiomycins that we have designated as napyradiomycin D1. Anti-infective and cytotoxic properties for all isolated compounds were evaluated against a set of pathogenic microorganisms and the HepG2 cell line, respectively. Among the new compounds, napyradiomycin D1 exhibited significant growth-inhibitory activity against methicillin-resistant Staphylococcus aureus, Mycobacterium tuberculosis, and HepG2.

Meroterpenoid natural products fromStreptomycesbacteria – the evolution of chemoenzymatic syntheses

“…It was isolated from the marine-derived Streptomyces sp. strain CA-271078, 31 and was not found to have antibacterial and antifungal properties on the cell lines tested. 18-Hydroxynapyradiomycin A1 (20), 18-oxonapyradiomycin A1 (21), 16-oxonapyradiomycin A2 (22) and 7-demethyl SF2415A3 (23) were all isolated from the culture broth of S. antimycoticus NT17.…”

“…It also showed moderate cytotoxic activities against HepG-2 (MIC = 27.1 μM).31 Napyradiomycin B4 (29) exhibited moderate activity against MRSA (MIC = 12-24 μg/mL) and M. tuberculosis H37Ra (MIC = 12-24 μg/mL). It also showed moderate cytotoxic activities against HepG-2 (MIC = 41.7 μM).31 Napyradiomycins B7a (30) and B7b (31) are epimers at the C-12 position of their dihydropyran ring, isolated from Streptomyces sp. strain CA-271078.…”

A Review: Halogenated Compounds from Marine Actinomycetes

“…strain CA-271078 yielded napyradiomycin analogs napyradiomycin B7a, napyradiomycin B7b and napyradiomycin D1 (13)(14)(15), which were cytotoxic against HepG-2 tumor cell line with IC 50 values of 41.7, 109.5 and 14.9 µM, respectively. Compounds 13 and 15 showed anti-bacterial activity against methicillin resistant Staphylococcus aureus (MRSA) and Mycobacterium tuberculosis with MIC values in the range of 12 to 48 µg/mL [13]. [14].…”

Progress in the Chemistry of Macrocyclic Meroterpenoids

“…A unique macrocyclic isoprenylated phenol, napyradiomycin D1 ( 16 ), containing a 14-membered cyclic ether ring, was isolated from Streptomyces sp. strain CA-271078 [ 25 ]. The authors report that meroterpenoid 16 ( Figure 5 ) exhibited significant inhibitory activity against methicillin-resistant Staphylococcus aureus , Mycobacterium tuberculosis and HepG2 .…”