Borrelidins C–E: New Antibacterial Macrolides from a Saltern-Derived Halophilic Nocardiopsis sp.

Abstract

Chemical investigation of a halophilic actinomycete strain belonging to the genus Nocardiopsis inhabiting a hypersaline saltern led to the discovery of new 18-membered macrolides with nitrile functionality, borrelidins C-E (1-3), along with a previously reported borrelidin (4). The planar structures of borrelidins C-E, which are new members of the rare borrelidin class of antibiotics, were elucidated by NMR, mass, IR, and UV spectroscopic analyses. The configurations of borrelidines C-E were determined by the interpretation of ROESY NMR spectra, J-based configuration analysis, a modified Mosher's method, and CD spectroscopic analysis. Borrelidins C and D displayed inhibitory activity, particularly against the Gram-negative pathogen Salmonella enterica, and moderate cytotoxicity against the SNU638 and K562 carcinoma cell lines.

New Borrelidins from Onchidium sp. Associated Streptomyces olivaceus SCSIO LO13

“…The structures of compounds 4 – 7 were readily identified as borrelidin A ( 4 ), borrelidin CR1 ( 5 ), borrelidin E ( 6 ) and borrelidin K ( 7 ) on the basis of comparisons of HR‐ESI‐MS, 1 H‐NMR, 13 C‐NMR data with those reported previously ( Figure ) …”

“…The borrelidins have attracted significant attention from the natural products community, and their noteworthy anti‐infective and cytotoxic activities have especially drawn the interest and efforts of biosynthetic and chemical synthesis researchers . In this study, three new borrelidins ( 1 – 3 ), along with four previously reported family members ( 4 – 7 ), were isolated from a likely associated symbiont S. olivaceus SCSIO LO13 from the marine pulmonated mollusk Onchidium sp.…”

“…Although borrelidin A ( 4 ) is toxic to non‐malignant cell types, its antitumor potential, as reflected in part by its ability to inhibit the growth of hepatocellular carcinoma cells, has garnered a significant amount of clinical interest . At the same time, a number of borrelidins with significantly improved cytotoxicities have been discovered and their activities correlated, at least in part, to specific structural modifications relative to borrelidin A ( 4 ) . In previous reports, we isolated borrelidins F–I from Streptomyces rochei SCSIO ZJ89 and some of these agents displayed significant cytotoxicities as well as anti‐metastasis activities …”

Bioactive compounds from marine Streptomyces sp.: Structure identification and biological activities

“…Further borrelidins (C-E) have been reported from the genus Nocardiopsis, displaying cidal effect, particularly against the Gram-negative pathogen Salmonella enterica, and moderate cytotoxicity against the SNU638 and K562 carcinoma cell lines. [27] Further new borrelidins F-I, but also, they were toxic, have been reported from mangrove-derived Streptomyces sp. [28] Ferulic acid.…”

Enhancement of Antibacterial Activity of Paludifilum halophilum and Identification of N-(1-Carboxy-ethyl)-phthalamic Acid as the Main Bioactive Compound

“…For instance, lajollamycin was isolated from the new strain Streptomyces nodosus [6], while salinosporamide A and borrelidins C-E were obtained from Salinispora tropica [13] and Nocardiopsis sp. [14], respectively. ese compounds are now a special target of several biotechnological industrial and academic institutions, since they possess a strong potential to be developed into pharmaceutical products [15].…”