Studies On The Secondary Metabolites Of Two Aspergillus Species And Their Bioactivities

Aspergillus distributes in all natural habitats,with richest speices in the fungal kingdom.In recent years,it has been a reaearching focus as the isolates of Aspergillus have produced a large number of bioactive secondary metabolites,including antimicrobial,antitumoral,antisecticidal,etc.Research results proved that Aspergillus is an important source of discovery of active drug lead compounds and novel compounds.Therefore,it is of great significance to further investigate the secondary metabolites from Aspergillus spp.In this thesis,two Aspergillus strains(YIM PH30711 and YIM PH30709)were selected by chemical diversity screening and biological activity assays from the fungal collections with 90 isolates obtained from soil samples of Qinghai-Tibet Plateau,China and New Delhi,India.Further investigations on the secondary metaboloites and their biological activities were developed.Herein,we report the characterization of the two Aspergillus isolates,the natural metabolite they produced,along with the bioactivities of the products.On the basis of morphological and genetical(ITS)characteristics,isolates YIM PH30711 and YIM PH30709 were identified as Aspergillus terreus and Aspergillus melleus,respectively.A.terreus produced 35 compouds in the PDB medium including nine new compounds and one new natural product(23).The new compounds were named as asterreusin A(1),demethyl-asterreusinA(2),asterreusin B(3),aspereusin B(4),aspereusin C(5),aspereusin D(6),aspereusin E(7),aspereusin A(8)and epiaspereusin A(9).Compounds 14,17,18 and 31,were found in Aspegillus fungus for the first time,and compounds 12 and 28 were obtained from A.terreus for the first time.Eleven compounds were obtained from the PDB culture of A.melleus and two new compounds,a pair of stereoisomers namely melleusin A(36)and melleusin B(37),were identified.The compounds were assayed with different bioactive models.Compounds 8 and 9 are a pair of diastereomers,but only compound 8 presented good inhibitory activity on acetylcholinesterase,the inhibition rate of AchE was 62.16%at 50 μM,indicating 4 P substituted has the key effect on its activity.Compounds 26 and 30 showed strong inhibition of HMG-CoA Reductase,with IC50 at 14.12 μM and 18.45 μM,respectively.