Chemical Investigation And Antiproliferative Evaluation Of The Secondary Metabolites Produced Byneosartorya Fischeri

Metabolites of microorganisms have long been regarded as a rich source of lead compounds for drug development.In this paper,chemical investigation and antiproliferative evaluation of the metabolites of Neosartorya fischeri CGMCC 3.5378 were performed,along with a discussion on the the biogenetic pathway of metabolites with unique chemical structures.Five new compounds neofipiperzines A-E(1-5)were isolated from the weal meal culture of N.fischeri CGMCC 3.5378,together with 16 known ones which were identified as spirotryprostatin F(6),TR-2(7),spirotryprostatin A(8),rel-(8S)-19,20-Dihydro-9,20-dihydroxy-8-methoxy-9,18-di-epi-fumitremorgin C(9),epi-aszonalenin C(10),verruculogen(11),12,13-dihydroxy-fumitremorgin C(12),fumitremorgin C(13),cyclouyprostatin B(14),dankasterone A(15),ergosterol(16),3-oxo-4,6,8(14),22-tetraunsaturated steroid(17),ergost-4-en-3,6-dione(18),(22E,24R)-24-methyl-6?-methoxy-5?-cholesta-7,22-diene-3?,5-diol(19),cyathisterol(20),and ergosterol peroxide(21).Structures of the new compounds were established based on IR,UV,MS,X-ray,1D-and 2D-NMR spectral analysis.All the twenty metabolites can be divided into two catalogs,namely indolyl diketopiperazines(1-14)and sterols(15-21).Compounds(1-3,5-8,10,11,13-15,17,18,20)were evaluated for their in vitro antiproliferative activity against MDA-MB-231,MCF-7,H1299 and HUVEC cell lines by MTT method.Compounds 15 showed the most potent activity with an IC50 value of 2.31±0.01 ?M,while compounds 17,18 and 20 exhibited moderate activities with IC50 values of 5.85±0.22?6.00±0.41 and 22.16±0.70 ?M respectively,against MDA-MB-231 cell line.