Study On The Second Metabolites And Bioactivities Of Penicillium Janthinellum And Fungi Of Pestalotiopsis Sp.

This paper is divided into three chapters.In the first chapter,the secondary metabolites isolated from Penicillium janthinellum and their biological activities were introduced.In the second chapter,the secondary metabolites of Pestalotiopsis sp.were studied.Chapter 3mainly reviews the research progress of secondary metabolites and pharmacological activities of Penicillium janthinellum up to now?1980-2019?.Penicillium janthinellum belongs to Penicillium,Capsidae and Cucurbitaceae.The secondary metabolites of Penicillium janthinellum mainly include indole diterpenoid alkaloids,azaphilones,epipolythiodiox-opiperazine?ETP?,alkaloids and BFA derivatives.In order to find more BFA derivatives,we studied the secondary metabolites of Penicillium janthinellum isolated from Youyang soil in Chongqing.Through rice fermentation culture,chromatographic separation and purification,and structural identification of various spectroscopic techniques,31 compounds were isolated,including 10 new compounds and 21known compounds.Among them,new compounds 1 and 2 are the first discovered BFA dimer and are a C-7 epimer;compound 3 possesses a?,?-unsaturated?-lactone ring,which is first discovered in BFA compound;compound 4,6,7 and 10 are ring-opening BFA derivatives,and compound 4 is a new BFA derivative of C-15 carbonyl group;compound 13 is a new indole diterpene alkaloid and compound 15 is a new dione.Piperazine alkaloids.Pestalotiopsis sp.belongs to the genus of asexual endophytic fungi of seminomycetes,which is an important economic asexual fungi.The secondary metabolites of this fungus are novel and complex,including terpenoids,alkaloids,polyketones and anthraquinones.They have many biological activities,such as anti-tumor,anti-virus,anti-bacterial and immunosuppressive activities.In this study,the secondary metabolites of a Pestalotiopsis sp.fungus isolated from Youyang soil in Chongqing were systematically studied.22 compounds were isolated from rice solid culture,including new compounds 1?polyketones?and 4?aromatic lactones?and 20 known compounds.In addition,we screened the pharmacological activities of some compounds isolated from Penicillium janthinellum.HL-60,U87MG,MDA-MB-231,A549,HEP-3B and SW480cell lines were selected to test the antineoplastic activity of compound 1-15.The results showed that compounds 1,2,8,9 and 15 had significant antineoplastic activity against these six cell lines,with IC₅₀ values ranging from 0.014 to 4.45 um.By comparing the antineoplastic activities of compounds 1-12,we found that the antineoplastic activities of BFA derivatives are closely related to the 13-membered lactone ring and the 4-OH configuration.This structure-activity relationship will be the key point for pharmacists to further explore the activities of BFA derivatives.Taking Staphylococcus aureus(CMCC?B?26003,Escherichia coli?ATCC25922?and Pseudomonas aeruginosa?ATCC27853?as experimental objects,the antimicrobial activity of compound 16-21 was tested.The results showed that compound 16 and 20 had certain inhibitory activity against Pseudomonas aeruginosa with MIC values of 16.0 and 32 ug/mL,respectively.In this paper,the secondary metabolites of Penicillium janthinellum and Pestalotiopsis sp.were systematically investigated,which led to the isolation of 53 compounds,including12 BFA series compounds,19 alkaloids and 22 others?12 new compounds and 41 known compounds?.Both the BFA dimers formed by an esterification between two BFA monomer units and the moiety?,?-unsaturated?-lactone ring were first discovered in naturally occurring BFA derivatives,which greatly enriched the BFA family structure and had a strong guiding significance for the future isolation of these compounds.The analysis of the structure-activity relationship demonstrated that the 13-membered lactone ring and the 4-OH configuration will significantly affect their anti-tumor activities.The in-depth study of the late biological activities of these compounds provides a scientific basis,and provides a research direction for the pharmaceutical preparation of these compounds.