Xanthoradones, new potentiators of imipenem activity against methicillin-resistant Staphylococcus aureus, produced by Penicillium radicum FKI-3765-2: I. Taxonomy, fermentation, isolation and biological properties

Abstract

The fungal strain FKI-3765-2, identified as Penicillium radicum, was found to produce potentiators of imipenem activity against methicillin-resistant Staphylococcus aureus (MRSA). Two new compounds, designated xanthoradones A and B, were isolated from the fermentation broth of the producing strain by solvent extraction, octadecyl silyl column chromatography and preparative HPLC. Xanthoradones A and B potentiated imipenem activity against MRSA by decreasing the MIC value of imipenem from 16 lg ml À1 to 0.060 and 0.030 lg ml À1 , respectively.

6'-Hydroxy-3'-methoxy-mitorubrin, a New Potentiator of Antifungal Miconazole Activity, Produced by Penicillium radicum FKI-3765-2

“…These results supported the molecular formula. The connectivity of proton and carbon atoms was established by the 13 C-1 H HSQC spectrum ( Table 2). Analyses of 1 H-1 H correlation spectroscopy (COSY) revealed the presence of one partial structure I, as shown in Fig.…”

“…Microorganisms P. radicum FKI-3765-2, previously reported as a xanthoradone-producing fungus, 13,14) was used for production of 1. The following seven microorganisms were used for antimicrobial tests: Bacillus subtilis ATCC 6633, Staphylococcus aureus FDA 209P, Micrococcus luteus PCI 1001, Escherichia coli NIHJ, Xanthomonas campestris pv.…”

“…As a result, we discovered various new compounds: actofunicone, 6) beauvericins, 7) citridones, 8,9) tensidoles 10) and citrinamides 11) from fungi and phenatic acids 12) from an actinomycete. From precise analysis of the metabolites of xanthoradone-producing Penicillium radicum FKI-3765-2, 13) a new compound, designated 6Ј-hydroxy-3Ј-methoxy-mitorubrin (1, Fig. 1), with a core structure different from that of xanthoradones 14) was isolated along with known 4Ј-hydroxy-3Ј-methoxy-(S)-mitorubrin 15) (2) and monomethyl-(S)-mitorubrin 16) (3).…”

Total synthesis of (±)-naphthacemycin A9, possessing both antibacterial activity against methicillin-resistant Staphylococcus aureus and circumventing effect of β-lactam resistance

“…On the basis of our anti-infective agents concept, originally proposed by S. Ōmura, 8 a screening system was established to identify microbial circumventors of imipenem resistance in MRSA, resulting in the isolation and structure determination of various natural products, including stemphones, 9 cyslabdan 10,11 and xanthoradones. 12,13 More recently, through continuous screening for new microbial circumventors of β-lactam resistance in MRSA in our laboratory, a culture broth of Streptomyces sp. KB-3346-5 exhibited very potent activity.…”

Xanthoradones, new potentiators of imipenem activity against methicillin-resistant Staphylococcus aureus, produced by Penicillium radicum FKI-3765-2 II. Structure elucidation

“…1 The taxonomy of the producing strain, fermentation, isolation and biological properties of the xanthoradones were described in a previous paper. 1 In this study, the physicochemical properties and structure elucidation of xanthoradones are described.…”