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

Using the OSMAC (One Strain Many Compounds) approach, the actinobacterium Streptomyces griseorubiginosus, 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 (1-23), wherein five compounds were unprecedented as natural products (19-23). Specifically, compounds 19 and 20 showcased novel anthrone backbones, while compound 23 displayed a distinctive tetralone structure. Additionally, compounds 21 and 22 presented an unusual naphtho [2,3-c]furan-4(9H)-one chromophore. Interestingly, the detection of all these novel compounds (19-23) was exclusively achieved when the bacterium was cultured in FA-1 liquid medium supplemented with the epigenetic modifier γ-butyrolactone. The elucidation of the structural features of the newfound compounds was accomplished through a combination of HRESIMS, 1D and 2D NMR spectroscopy, as well as QM-NMR (Quantum Mechanical-Nuclear Magnetic Resonance) methods and by comparison with existing literature. Moreover, the determination of the relative configuration of compound 23 was facilitated by employing the mix-J-DP4 computational approach.

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. At 1 µg/mL, five compounds synergised with PMB and inhibited the growth of B. cenocepacia by ≥70% compared with growth in PMB alone. Follow-up testing revealed that one compound from the screen, the aminocoumarin antibiotic novobiocin, synergised with PMB and colistin against tobramycin-resistant clinical isolates of B. cenocepacia and Burkholderia multivorans. In parallel, we show that novobiocin sensitivity is common among BCC species and that these bacteria are even more susceptible to an alternative aminocoumarin, clorobiocin, which also had an additive effect with PMB against B. cenocepacia. These studies support using aminocoumarin antibiotics to treat BCC infections and show that synergisers can be found to increase the efficacy of antimicrobial peptides and polymyxins against BCC bacteria.

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.