Cell-adhesion Inhibitors Produced by a Sea Hare-derived Periconia sp.

Abstract

Peribysin J and macrosphelide M have been isolated from a strain of Periconia byssoides originally isolated from the sea hare Aplysia kurodai. Their absolute stereostructures have been elucidated on the basis of spectroscopic analyses using 1D and 2D NMR techniques and some chemical transformations including the modified Mosher's method. These fungal metabolites inhibited the adhesion of human-leukemia HL-60 cells to humanumbilical-vein endothelial cells (HUVEC).Keywords fungus, cell-adhesion inhibitor, peribysin, macrosphelide, Periconia sp. IntroductionBased on the fact that some of the bioactive materials isolated from marine animals have been produced by bacteria, we have turned our attention to new antitumour materials from microorganisms inhabiting the marine environment [1ϳ3]. As part of this study, we have previously isolated the cell-adhesion inhibitors, macrosphelides EϳI, L [4, 5] and peribysins AϳI [6ϳ8], from a strain of Periconia byssoides OUPS-N133 originally isolated from the sea hare Aplysia kurodai. All of these compounds, except for macrosphelide I, inhibited the adhesion of human-leukemia HL-60 cells to human-umbilical-vein endothelial cells (HUVEC) more potently than herbimycin A [9,10]. Further investigation of the metabolites from this fungal strain has now led to the isolation of new antiadhesion compounds designated peribysin J (1) and macrosphelide M (2) (Fig. 1). We describe herein the absolute stereostructures of 1 and 2 (Fig. 1) in addition to their inhibition of cell adhesion. Results and DiscussionThe fungal strain was cultured at 27°C for 4 weeks in a medium containing malt extract 1.0%, glucose 1.0% and peptone 0.05% in artificial seawater adjusted to pH 7.5, as reported previously [4ϳ8]. The AcOEt extract of the culture filtrate was purified by chromatography on Sephadex LH-20 and silica gel by reversed phase HPLC to afford 1 and 2. The physico-chemical properties of these compounds are summarized in Table 1.1 had the molecular formula C 15 H 26 O 5 established by the [M] ϩ peak of 1 in high-resolution electron-impact mass spectrometry (HREI-MS). Its IR spectrum exhibited bands at 3384 and 1653 cm

Terpenes from Marine-Derived Fungi

“…Peribysins A–J ( 18 – 27 ) are a group of eremophilane-type sesquiterpenoids produced by Periconia byssoides which was isolated from the sea hare Aplysia kurodai [18–21]. They have raised considerable interest and have become the subject of synthetic efforts due to their ability of inhibit the adhesion of human-leukemia HL-60 cells to HUVEC at lower μM concentration, and thus are two orders of magnitude more potent than the standard control in this assay system, herbimycin A.…”

Binary fluorous tagging enables the synthesis and separation of a 16-stereoisomer library of macrosphelides

“…If macrosphelide D has the same configurations at the pairs of adjacent stereocenters as macrosphelides A and E, then it could be either 10 (C3 S) or 11 (C3 R). Structure 11 is already a known natural product called macrosphelide M. 33 Unfortunately, the spectra of macrosphelide D are reported in chloroform- d 1 and those of macrosphelide M are in acetone- d 6 , so we could not assess at this point whether the two natural samples are the same or different. However, since macrosphelides A and D were isolated from the same broth, the structure 10 seems more likely than 11 .…”

Pericoterpenoid A, a new bioactive cadinane-type sesquiterpene fromPericoniasp.

“…They are also known and widely studied because some species belonging in it are responsible for severe diseases of cereal crops such as milo disease [2]. Previous chemical investigations have shown that the genus Periconia is a rich source of terpenes, including monoterpene [3], sesquiterpenes [4][5][6][7], and diterpenes [8]. In our ongoing search for bioactive secondary metabolites from endolichenic fungi, a chemical investigation focused on a strain of this genus (19-4-2-1) was carried out, which led to the isolation of a new cadinane-type sesquiterpene, namely pericoterpenoid A (1).…”