OSMAC Approach and Cocultivation for the Induction of Secondary Metabolism of the Fungus .

The application of an OSMAC (One Strain-Many Compounds) approach on the fungus , isolated from a soil sample collected on the coast of Asturias (Spain), using different culture media, chemical elicitors, and cocultivation techniques resulted in the isolation and identification of nine new compounds (, , , -, ), along with 15 known ones (-, , , , -). Compounds - were detected in fungal extracts from JSA liquid fermentation, compounds - were isolated from a solid rice medium, whereas compounds and were isolated from a solid wheat medium. Addition of 5-azacytidine to the solid rice medium caused the accumulation of compounds -, whereas adding -acetyl-d-glucosamine triggered the production of two additional metabolites, and .

Induction of New Aromatic Polyketides from the Marine Actinobacterium through an OSMAC Approach.

Using the OSMAC (One Strain Many Compounds) approach, the actinobacterium , derived from an unidentified cnidarian collected from a reef near Pointe de Bellevue in Réunion Island (France), was subjected to cultivation under diverse conditions. This endeavour yielded the isolation of a repertoire of 23 secondary metabolites (-), wherein five compounds were unprecedented as natural products (-). Specifically, compounds and showcased novel anthrone backbones, while compound displayed a distinctive tetralone structure.

Anthraquinones as Inhibitors of SOS RAS-GEF Activity.

Recent breakthroughs have reignited interest in RAS GEFs as direct therapeutic targets. To search for new inhibitors of SOS GEF activity, a repository of known/approved compounds (NIH-NACTS) and a library of new marine compounds (Biomar Microbial Technologies) were screened by means of in vitro RAS-GEF assays using purified, bacterially expressed SOS and RAS constructs. Interestingly, all inhibitors identified in our screenings (two per library) shared related chemical structures belonging to the anthraquinone family of compounds.

Identification of synergists that potentiate the action of polymyxin B against Burkholderia cenocepacia.

Burkholderia cenocepacia and other members of the Burkholderia cepacia complex (BCC) are highly multidrug-resistant bacteria that cause severe pulmonary infections in patients with cystic fibrosis. A screen of 2686 compounds derived from marine organisms identified molecules that could synergise with polymyxin B (PMB) to inhibit the growth of B. cenocepacia.

The marine fungal metabolite, AD0157, inhibits angiogenesis by targeting the Akt signaling pathway.

In the course of a screening program for the inhibitors of angiogenesis from marine sources, AD0157, a pyrrolidinedione fungal metabolite, was selected for its angiosupressive properties. AD0157 inhibited the growth of endothelial and tumor cells in culture in the micromolar range. Our results show that subtoxic doses of this compound inhibit certain functions of endothelial cells, namely, differentiation, migration and proteolytic capability.

Antiangiogenic versus cytotoxic activity in analogues of aeroplysinin-1.

A series of analogues of the potentially angiogenic inhibitor aeroplysinin-1 1 were synthesized and their in vitro antiangiogenic and cytotoxic activities evaluated. In the case of epoxy ketone 6 and azlactone 36 the relationship sprouting inhibition assay/cytotoxicity in BAE cells was enhanced by one order and two orders of magnitude, respectively, with respect to the reference. These results imply more specific antiangiogenic properties for the synthesized derivatives.