Endophytic fungi associated with Sudanese medicinal plants show cytotoxic and antibiotic potential.

In this study, we isolated 15 endophytic fungi from five Sudanese medicinal plants. Each fungal endophytic strain was identified by sequencing of internal transcribed spacer (ITS) regions of rDNA. Ethyl acetate extracts were prepared from each endophyte cultivated in vitro and tested for their respective antibacterial activities and antiproliferative activities against human cancer cells. Antibacterial screening was carried out against two bacterial strains: Gram-negative Escherichia coli and Gram-positive methicillin-resistant Staphylococcus aureus, by the broth dilution method. Cell viability was evaluated by the MTT procedure after exposure of MCF7 breast cancer cells and HT29 or HCT116 human colon adenocarcinoma cells to each endophytic extract. Of interest, Byssochlamys spectabilis isolated from Euphorbia prostata showed cytotoxicity (IC50 = 1.51 ± 0.2 µg mL(-1)) against MCF7 cells, but had a low effect against HT29 or HCT116 cells (IC50 > 20 µg mL(-1)). Cladosporium cladosporioides 2, isolated from Vernonia amygdalina leaves, showed antiproliferative activities against MCF7 cells (IC50 = 10.5 ± 1.5 µg mL(-1)) only. On the other hand, B. spectabilis and Alternaria sp. extract had antibacterial activities against the S. aureus strain. The findings of this work revealed that endophytic fungi associated with medicinal plants from Sudan could be considered as an attractive source of new therapeutic compounds.

Synthesis and antioxidant potential of novel synthetic benzophenone analogues.

Considering that oxidative stress is strongly implicated in the toxicity of chemotherapy, much effort is focused on the research of diverse antioxidants as protective agents. An efficient synthesis of three novel benzophenones containing 1,3-thiazol moiety (6a-c) is described. Their antioxidant power was evaluated in vitro and in three cell lines (the cancerous MCF7 and the non-cancerous hTERT-HME1 mammary cells, and the H9c2 cardiomyoblastic cells). One analogue 5-(2,5-dihydroxybenzoyl)-2(3H)-benzothiazolone (6c), displayed an important antioxidant activity, a low cytotoxicity, and could decrease reactive oxygen species production generated by tert-butyl hydroperoxide (tBHP) in all three cell lines. Interestingly, 6c was able to protect the non-cancerous cells against tBHP-induced death. Further studies are underway to determine its relevance as an adjuvant in oxidative stress inducing chemotherapy.

Cytoprotective effects of 5 benzophenones and a xanthone from Hypericum annulatum in models of epirubicin-induced cytotoxicity: SAR-analysis and mechanistic investigations.

A new benzophenone O-glucoside neoannulatophenonoside (1) together with the known pinocembrin-7-O-glucoside were isolated from the aerial parts of Hyperium annulatum Moris (Guttiferae). The former was identified as 3',5',6-trihydroxy-4-methoxybenzophenone-2-O-beta-D-glucopyranoside by means of chemical and physical evidence. The cytoprotective effects of the new compound together with the previously isolated from this species hypericophenonoside (2), annulatophenone (3), annulatophenonoside (4), acetylannulatophenonoside (5) and 1,3,7-trihydroxyxanthone (6) were evaluated in a model of epirubicin-induced cellular toxicity in K-562 cells. While the benzophenone O-glycosides 1, 2, 4 and 5 exerted substantial cytoprotective effects against the epirubicin cytotoxicity in K-562 cells the aglycones 3 and 6 lacked any significant cytoprotective activity. Biochemical investigations aimed at evaluating the free-radical scavenging activity of the tested compounds as well as their effects on the cellular glutathione stores were carried out as well, aiming at unravelling the mechanisms of cytoprotection. Finally, the ability of 1, 4 and 5 to ameliorate epirubicin-induced anticlonogenic effects on bone marrow cells colony forming units, in vitro were also evaluated. Taken together, the experimental data indicate that the benzophenone glycosides isolated from H. annulatum have a substantial cytoprotective potential against the toxic effects induced by epirubicin and necessitates further detailed pharmacological evaluation of these compounds as possible chemoprotective/radioprotective agents.