Napyradiomycin A4 and Its Relate Compounds, a New Anti-PRV Agent and Their Antibacterial Activities, from Streptomyces kebangsaanensis WS-68302.

Two new napyradiomycins derivatives, napyradiomycin A4 (1) and A80915 H (2), along with five known ones, were isolated from the ethyl acetate extract of fermentation culture of Streptomyces kebangsaanensis WS-68302. Their structures were elucidated by extensive spectroscopic analysis, including HR-MS, 1D and 2D NMR, CD spectrum, as well as comparison with literature data. Compound 1 exhibited significant antiviral activity against PRV (Pseudorabies virus) with an IC50 value of 2.056 µM and therapeutic ratio at 14.98, suggesting that it might have potential for development of an antiviral agent. Moreover, compound 1 displayed the strongest inhibition against PRV protein among the tested napyradiomycins in the indirect immunofuorescence assay. Compounds 3 and 4 showed higher activities against swine pathogenic Streptococcus suis than the positive control penicillin G sodium salt, with MIC values of 3.125 and 6.25 µg/mL, respectively. Compounds 1 and 3-6 exhibited moderate antibacterial activity against the swine pathogenic Erysipelothrix rhusiopathiae, with MIC values ranging from 25 to 50 µg/mL.

Antifouling Napyradiomycins from Marine-Derived Actinomycetes Streptomyces aculeolatus.

The undesired attachment of micro and macroorganisms on water-immersed surfaces, known as marine biofouling, results in severe prevention and maintenance costs (billions €/year) for aquaculture, shipping and other industries that rely on coastal and off-shore infrastructures. To date, there are no sustainable, cost-effective and environmentally safe solutions to address this challenging phenomenon. Therefore, we investigated the antifouling activity of napyradiomycin derivatives that were isolated from actinomycetes from ocean sediments collected off the Madeira Archipelago. Our results revealed that napyradiomycins inhibited ≥80% of the marine biofilm-forming bacteria assayed, as well as the settlement of Mytilus galloprovincialis larvae (EC50 < 5 µg/ml and LC50/EC50 >15), without viability impairment. In silico prediction of toxicity end points are of the same order of magnitude of standard approved drugs and biocides. Altogether, napyradiomycins disclosed bioactivity against marine micro and macrofouling organisms, and non-toxic effects towards the studied species, displaying potential to be used in the development of antifouling products.

New Napyradiomycin Analogues from Streptomyces sp. Strain CA-271078.

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.

Cytotoxic and Antimicrobial Napyradiomycins from Two Marine-Derived, MAR 4 Streptomyces Strains.

Cancer cell cytotoxicity-guided fractionation of the acetone extracts of two cultured marine-derived Streptomyces strains belonging to the MAR4 group yielded six new napyradiomycins, compounds A-F (1-6), together with three known compounds, napyradiomycins B2-B4 (7-9). Napyradiomycins 1-4 are new members of the napyradiomycin "C type" meroterpenoids that possess a linear monoterpene moiety bridging between C-7 and C-10a. Compound 4 has an additional tetrahydropyran ring fused to the phenol moiety. Compounds 5-9 are related to the napyradiomycin "B type" meroterpenoids. The structures of all new compounds were assigned by interpretation of 1D and 2D NMR, MS and other spectroscopic data. The relative configurations were assigned based upon interpretation of ROESY 2D NMR experiments. The cytotoxicity of 1-9 against the human colon carcinoma cell line HCT-116, and their antibacterial activities against Methicillin-resistant Staphylococcus aureus (MRSA) are presented.