Antitumor Metabolites from Fungus Aspergillus sydowi D2-6

OBJECTIVE To investigate the antitumor metabolites from fungus Aspergillus sydowi D 2-6.METHODS The strain D 2-6 was fermented in a rotary shaker and the bioactive metabolites in the fermentation broth were isolated through a bioassay-guided separation procedure.Structures of the bioactive compounds were determined on the basis of physicochemical and spectroscopic data.The antitumor activity of the compounds against various tumor cell lines(K562,A549,BEL7402,HL60 and P388) in vitro was assayed by MTT method,accompanied with cell morphological observation under light microscope.RESULTS Eight compounds were isolated from the fermentation broth of Aspergillus sydowi D 2-6,and identified as five diketopiperazine derivatives including fumitremorgin B(1),dihydroxy-fumitremorgin C(2),demethoxy-fumitremorgin C(3),fumitremorgin C(4),gliotoxin(5),one quinazoline derivative fumiquinazoline C(6),two hetero-spirocyclic γ-lactam derivatives azaspirofuran A(7) and azaspirofuran B(8).Antitumor activity assay displayed that compound 5 had the strongest inhibitory activity on test cell lines among the detected compounds.Compound 5 inhibited the growth of P388,A549 and K562 cells with IC50 of 1.47,0.10 and 0.57 nmol·L-1,respectively.Compound 7 inhibited the proliferation of P388,A549 and BEL7402 cells with IC50 of 31.43,0.01 and 28.71 μmol·L-1,respectively.Compound 6 inhibited the growth of K549 cells with IC50 of 42.10 μmol·L-1.CONCLUSION The predominant antitumor metabolites from Aspergillus sydowi D 2-6 were sulphureous diketopiperazine,hetero-spirocyclic γ-lactam and quinazoline derivatives,among which compound 5 showed strong inhibition on P388,A549 and K562 cells,while compound 7 exhibited specific inhibitory activity on A549 cells.