Amal H. Aly

Bioactive natural products from endophytic fungi, isolated from higher plants, are attracting considerable attention from natural product chemists and biologists alike as indicated by the steady increase of publications devoted to this topic during recent years (113 research articles on secondary metabolites from endophytic fungi in the period of 2008–2009, 69 in 2006–2007, 36 in 2004–2005, 14 in 2002–2003, and 18 in 2000–2001). This overview will highlight the chemical potential of endophytic fungi with focus on the detection of pharmaceutically valuable plant constituents, e.g. paclitaxel, camptothecin and podophyllotoxin, as products of fungal biosynthesis. In addition, it will cover new bioactive metabolites reported in recent years (2008–2009) from fungal endophytes of terrestrial and mangrove plants. The presented compounds are selected based on their antimicrobial, antiparasitic, cytotoxic as well as neuroprotective activities. Furthermore, possible factors influencing natural product production in endophytes cultivated in vitro and hence the success of bioprospecting from endophytes are likewise discussed in this review.

Marine bacteria and fungi are of considerable importance as new promising sources of a huge number of biologically active products. Some of these marine species live in a stressful habitat, under cold, lightless and high pressure conditions. Surprisingly, a large number of species with high diversity survive under such conditions and produce fascinating and structurally complex natural products. Up till now, only a small number of microorganisms have been investigated for bioactive metabolites, yet a huge number of active substances with some of them featuring unique structural skeletons have been isolated. This review covers new biologically active natural products published recently (2007-09) and highlights the chemical potential of marine microorganisms, with focus on bioactive products as well as on their mechanisms of action.

From the Egyptian medicinal plant Polygonum senegalense the fungal endophyte Alternaria sp. was isolated. Extracts of the fungus grown either in liquid culture or on solid rice media exhibited cytotoxic activity when tested in vitro against L5178Y cells. Chromatographic separation of the extracts yielded 15 natural products, out of which seven were new compounds, with both fungal extracts differing considerably with regard to their secondary metabolites. Compounds 1, 2, 3, 6, and 7 showed cytotoxic activity with EC 50 values ranging from 1.7 to 7.8 microg/mL. When analyzed in vitro for their inhibitory potential against 24 different protein kinases, compounds 1- 3, 5- 8, and 15 inhibited several of these enzymes (IC 50 values 0.22-9.8 microg/mL). Interestingly, compounds 1, 3, and 6 were also identified as constituents of an extract derived from healthy leaves of the host plant P. senegalense, thereby indicating that the production of natural products by the endophyte proceeds also under in situ conditions within the plant host.