Lambertellin

The 'Lambertellin system' was disclosed which rationally explains the fungal replacement (mycoparasitism) of Monilinia fructigena (M. f., the host) with Lambertella corni-maris (L. corni-maris, the parasite) without competitive inhibition in the simultaneous incubations on agar media. The 'Lambertellin system' involves; (a) L. corni-maris secretes nontoxic lambertellols (1, 2) as the diffusible precursors of the authentic responsible substance 3 regardless of existence of the host M. f.; (b) In the absence of the host, the environment around the parasite is kept under neutral condition, and both 1 and 2 are readily transformed into 3; (c) Lambertellin (3) inhibits not only the host but also the parasite. The parasite degrades 3 for detoxification; and (d) Upon the host M. f. approaching closely to the area where the parasite inhabits, the environment around the parasite becomes acidic to stabilize 1 and 2, which gives them a chance to diffuse into the host area. Then these are gradually transformed into 3 to inhibit the host without damaging the parasite. This mechanism also accords with the progress of 'Natsu-Nenju' disease on apple fruits, which is known to be a mysterious phyto-disease because of two unique stages of its lifecycle, anamorphic (asexual) and teleomorphic (sexual). The 'Lambertellin system' would be categorized as a novel class of alleropathies.

A novel and efficient method has been developed for the synthesis of highly functionalized benzo[g]- and dihydropyrano[2,3-g]chromene derivatives via addition and subsequently cyclization of 2-hydroxynaphthalene-1,4-dione or 2,5-dihydroxycyclohexa-2,5-diene-1,4-dione to the condensation product of an aldehyde with malononitrile in the presence of a catalytic amount of Et(3)N in CH(3)CN at ambient temperature. The procedures are very facile. The products can be obtained with simple filtration in high yields, and no more purification is needed. These compounds are closely related to ring systems such as beta-lapachone, alpha-xiloidone, lambertellin, pyranokunthone B, and WS-5995A, which have a broad spectrum of biological activities.

Lambertellin (1) and ergosta-5,7,22-trien-3-ol (2) were isolated from the solid rice fermentation of the plant pathogenic fungus Pycnoporus sanguineus MUCL 51321. Their structures were elucidated using comprehensive spectroscopic methods. The isolated compounds were tested on lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. Lambertellin (1) exhibited promising inhibitory activity against nitric oxide (NO) production with IC50 value of 3.19 µM, and it significantly inhibited the expression of inducible NO synthase (iNOS) and cyclooxygenase 2 (COX-2). Lambertellin (1) also decreased the expression of pro-inflammatory cytokines IL-6 and IL-1β. The study of the mechanistic pathways revealed that lambertellin (1) exerts its anti-inflammatory effect in LPS-stimulated RAW 264.7 macrophage cells by modulating the activation of the mitogen activated protein kinase (MAPK) and nuclear factor κB (NF-κB) signaling pathways. Therefore, lambertellin (1) could be a promising lead compound for the development of new anti-inflammatory drugs.