Epstein-Barr virus (EBV) is a member of the γ-herpes virus subfamily and has been implicated in the pathogenesis of several human malignancies. Bioassay-guided fractionation was conducted on an EtOAc-soluble extract of the roots of Saururus chinensis and monitored using an EBV lytic replication assay. This led to the isolation of 19 new (1-19) and nine known (20-28) lignans. The absolute configurations of the new lignans were established by Mosher's ester, ECD, and computational methods. Eight lignans, including three sesquineolignans (19, 23, and 24) and five dineolignans (3, 4, 26, 27, and 28), exhibited inhibitory effects toward EBV lytic replication with EC50 values from 1.09 to 7.55 μM and SI values from 3.3 to 116.4. In particular, manassantin B (27) exhibited the most promising inhibition, with an EC50 of 1.72 μM, low cytotoxicity, CC50 > 200 μM, and SI > 116.4. This is the first study demonstrating that lignans possess anti-EBV lytic replication activity.
Four new 3,5-diarylpyrazole analogues (1-4) were isolated from an extract of the flowers of Chrysanthemun indicum using a combination of ammonolysis of the total flavonoid extract and an Aβ aggregation inhibitory activity guided purification procedure. All four compounds (1-4) showed moderate to potent activity against Aβ aggregation with EC50 values of 4.3, 15.8, 1.3, and 2.9 μM, respectively. Moreover, compound 3 showed low cytotoxicity and significant neuroprotective activity against Aβ-induced cytotoxicity in the SH-SY5Y cell line. This report is the first to show that 3,5-diarylpyrazole analogues can inhibit Aβ aggregation and exhibit neuroprotective activity with potential for the treatment of Alzheimer's disease. Taken together, the method presented here offers an alternative approach to yield bioactive compounds.
This review presents an account of the microbial biodiscovery methodology developed and applied in our laboratory at The University of Queensland, Institute for Molecular Bioscience, with examples drawn from our experiences studying natural products produced by Australian marine-derived (and terrestrial) fungi and bacteria.
Bioassay-guided fractionation was conducted on an EtOAc-soluble extract of the whole plants of Scutellaria barbata, monitored by inhibition of Epstein-Barr virus (EBV) lytic replication. Twenty-six neo-clerodane diterpenoids were isolated, of which 13 are new (1-13, scutolides A-L) and 13 previously known (14-26). The structures of 1-13 were elucidated by analysis of their NMR and MS spectroscopic data. Furthermore, the configurations of the new compounds 1 and 11 were confirmed by single-crystal X-ray diffraction. All of the isolated compounds were evaluated for inhibitory effects against EBV lytic replication. Eleven compounds (3, 4, 6, 11, 12, 15, 16, 17, 20, 22, and 24) exhibited moderate to potent inhibition, with EC50 values from 3.2 to 23.6 μM and selective index (SI) values from 2.1 to 109.2. More specifically, the new compound 4 showed the most potent activity, with EC50 and SI values of 3.2 μM and 46.1, respectively, while compound 24 (EC50 = 16.4 μM) exhibited the highest SI of 109.2. This study is the first to report that neo-clerodane diterpenoids demonstrate significant inhibition against EBV lytic replication.
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