Two acid sorbicillin analogues from saline lands-derived fungus Trichoderma sp.

Abstract

Two new acid sorbicillin analogues, (E)-6-(2,4-dihydroxyl-5-methylphenyl)-6-oxo-2-hexenoic acid (1) and 6-(2,4-dihydroxyl-5-methylphenyl)-6-oxohexanoic acid (2), together with 12 known compounds, were isolated from a saline lands-derived fungus Trichoderma sp. The structures of the new compounds were established by interpretation of their spectroscopic data. Their cytotoxic effects on P388 and HL-60 cell lines were preliminarily evaluated by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) method. Furthermore, the new compounds exhibited weak radical scavenging activity against DPPH (1,1-diphenyl-2-picrylhydrazyl). The Journal of Antibiotics (2011) 64, 645-647; doi:10.1038/ja.2011; published online 20 July 2011Keywords: cytotoxicity; fungus; sorbicillinoids; Trichoderma sp. INTRODUCTIONFungi of the genus Trichoderma are ubiquitous in the environment. In recent years, more and more attention has been paid to them because of a wide range of prospective utility 1 as biological control agents to suppress different fungal plant pathogens and to promote plant growth and for producing commercial enzymes, such as cellulases, hemicellulases, proteases and b-1,3-glucanase. 2 At the same time, many structurally novel and biologically active secondary metabolites have been reported from the species. For example, peptibols, 3 which are linear peptides characterized by an acetylated N-terminus, showed cytotoxic, membraneperturbing and antibiotic activities. Trichocaranes 4 A-D, isolated from Trichoderma virens, significantly inhibited the growth of etiolated wheat coleoptiles. In addition, a series of sorbicillin-related compounds 5-7 from Trichoderma showed moderate radical scavenging activity.In our search for cytotoxic compounds from fungi, a Trichoderma sp. was isolated from the saline lands soil collected along the coast of Bohai Bay in Zhanhua, Shandong Province, China. Its extract showed moderate activity to brine shrimp. The isolation work led to the finding of two new compounds (E)-6-(2,4-dihydroxyl-5-methylphenyl)-6-oxo-2-hexenoic acid (1) and 6-(2,4-dihydroxyl-5-methylphenyl)-6-oxohexanoic acid (2), along with 12 known ones, which were trichodimerol, bisvertinolone, adenosine, ergosterol, ergosterol peroxide, cerevisterol, 3b,5a-dihydroxy-6b-methoxyergosta-7,22-diene, (22E,24R)-5a,6a-epoxyergosta-8,22-diene-3b,7a-respectively. The known compounds were identified by comparison with previously reported physical and spectral data. In this paper, we reported the new compounds' isolation, structure elucidation, cytotoxic activities to P388 and HL-60 cell lines and radical scavenging activity against DPPH (1,1-diphenyl-2-picrylhydrazyl) (Figure 1).

Chemical Composition of an Aphid Antifeedant Extract from an Endophytic Fungus, Trichoderma sp. EFI671

“…Extracts of Trichoderma sp. isolated from saline lands contained ergosterol and ergosterol peroxide along with other sterol compounds and two new sorbicillin acid analogs [39]. Ergosterol, stigmasterol and β-sitosterol have been isolated from two strains of T. harzianum [40].…”

Constitutive hyperproduction of sorbicillinoids in Trichoderma reesei ZC121

“…Moreover, they could be utilized as pigments and food colorants (yellow pigments) as well. Since they were first discovered in 1948 from Penicillium notatum [ 51 ], studies related to sorbicillinoids have focused on finding new compounds with similar structure [ 52 ], elucidating chemical structures and biological activities [ 16 , 50 ], establishing the complex biosynthetic pathway [ 41 ] and developing chemical synthesis methods [ 53 ]. However, both strain engineering to increase sorbicillinoids’ production and the relevant regulatory mechanism is less studied.…”

Sorbicillinoids from Fungi and Their Bioactivities

“…They have highly diverse bioactivities and have been isolated from either marine [2][3][4] or terrestrial fungi [5][6][7]. Many of them possess elaborate bicyclic or tricyclic systems that appear to arise from the oxidative dearomatizaton and subsequent dimerization/trimerization of sorbicillin (5).…”