Identification and Bioactivities of Secondary Metabolites Derived from Endophytic Fungi Isolated from Ethnomedicinal Plants of Tujia in Hubei Province:A Review

Tujia is a national minority,inhabiting in the mountainous Wuling area in China.Since 1978,Tujia medicine has been studied,summarized and developed,leading to numerous achievements by Chinese researchers,such as the publishing of approximately 30 monographs of Tujia medicine.These publications are focused on summarizing and improving the theory of Tujia medicine and developing clinical therapies from this system of medicine.The shortage of natural medicinal plants used in Tujia medicine has created the need to discover new resources to replace them and protect endangered natural plant species.Endophytic fungi are one of the conservation options,are considered a source of new bioactive natural products,and are a renewable and inexhaustible source of new drugs and agrochemicals.This review summarizes 260 compounds from endophytic fungi that have been previously isolated from the medicinal plants of Tujia.These compounds include steroids,terpenoids,meroterpenoids,polyketides,alkaloids,peptides,aliphatic compounds,aromatic compounds,and heterocyclic compounds.

Chemical investigation on the cultures of the fungus Xylaria carpophila

A chemical investigation on the cultures of Xylaria carpophila led to the isolation of one known cyclopeptide cyclo(N-methyl-L-Phe-L-Pro-L-Leu-D-Ile-L-Val)(1),five new sesquiterpenes,named as xylcarpins A-E(2-6),and another known compound(7).The structures were determined by extensive NMR and MS spectroscopic analysis.The absolute configuration of 1 was established by use of Marfey’s method and ROESY spectroscopic data.All compounds were tested for their cytotoxicities against five human cancer cell lines.Compound 7 showed week inhibitory activity.

Guajadials C-F, four unusual meroterpenoids from Psidium guajava

Guajadials C-F(1-4),four sesquiterpenoid-based meroterpenoids with unprecedented skeletons were isolated from the leaves of Psidium guajava.Their structures and relative configurations were established by extensive spectroscopic analysis.A possible biosynthetic pathway for 1-4 was also proposed.

ent-Kaurane diterpenoids from the plant Wedelia trilobata

Four new ent-kaurane diterpenoids,namely,3α-tigloyloxypterokaurene L_(3)(1),ent-17-hydroxy-kaura-9(11),15-dien-19-oic acid(2),and wedelobatins A(3)and B(4),together with 11 known ent-kaurane diterpenoids(5-15),were isolated from the ethanol extract of Wedelia trilobata.All the structures of 1-15 were elucidated on the basis of spectroscopic studies.

Two novel fomannosane-type sesquiterpenoids from the culture of the basidiomycete Agrocybe salicacola

Two novel fomannosane-type sesquiterpenoids,agrocybins H(1)and I(2),together with a known compound illudosin(3),were isolated from the culture broth of the mushroom Agrocybe salicacola.Their structures were elucidated by extensive spectroscopic analysis.The relative stereochemistry of 1 was determined by the use of single crystal X-ray crystallographic diffraction.

Six novel steroids from culture of basidiomycete Polyporus ellisii

Investigation of the culture of basidiomycete Polyporus ellisii led to the isolation of a novel compound 3β,9α,15α-trihydroxy-(22E,24R)-10(5→4)-abeo-ergosta-6,8(14),22-trien-5-one(1)with a new 5/7/6/5 ring system of ergosterol skeleton.In addition,five new steroids,5β,6β-epoxy-3β,7α,9α-trihydroxy-(22E,24R)-ergosta-8(14),22-dien-15-one(2),5β,6β-epoxy-3β,7α-dihydroxy-(22E,24R)-ergosta-8(14),22-dien-15-one(3),5α,6α-epoxy-3β,9α,15α-trihydroxy-(22E,24R)-ergosta-8(14),22-dien-7-one(4),15α-acetoxy-(22E,24R)-ergosta-4,6,8(14),22-tetraen-3-one(5),15β-methoxy-(22E,24R)-ergosta-4,6,8(14),22-tetraen-3-one(6),along with four known ergosterols(7-10),were obtained.All structures were elucidated based on 1D and 2D NMR spectral data.New compounds were evaluated for cytotoxicity against five human cancer cell lines,only compound 4 was found to exhibit a favorable cytotoxicity profile toward all tested tumor cell lines.

Lanostane Triterpenoids from Fruiting Bodies of Ganoderma leucocontextum

Six new lanostane-type triterpenoids,namely leucocontextins S-X(1-6),together with twelve known compounds,were isolated from the fruiting bodies of Ganoderma leucocontextum.Their structures were established by MS and NMR data.

Three New Humulane Sesquiterpenes from Cultures of the Fungus Antrodiella albocinnamomea

Three new humulane-type sesquiterpenes,antrodols A–C(1–3),were isolated from cultures of the fungus Antrodiella albocinnamomea.Their structures were elucidated on the basis of extensive spectroscopic analysis.Antrodols A–C(1–3)are first examples of humulane-type sesquiterpenes isolated from cultures of higher fungi,and antrodol A(1)was the first report of humulane-type sesquiterpene with a methyl rearranged at C-3.All compounds were evaluated in the enzyme inhibition assay against two protein-tyrosine phosphatases(PTPs):MEG2 and PTP1Bc.

Seven New Drimane-Type Sesquiterpenoids from Cultures of Fungus Phellinus tuberculosus

Seven new drimane-type sesquiterpennoids,phellinuins A-G(1-7),together with one known compound 3b,11,12-trihydroxydrimene(8)were isolated from the cultures of mushroom Phellinus tuberculosus.Their structures were elucidated on the basis of NMR and MS spectroscopic data and by comparison with data reported in the literature.

Steroids and Sesquiterpenes From Cultures of the Fungus Phellinus igniarius

Two new steroids,3a,17a,19,20-tetrahydroxy-4a-methylpregn-8-ene(1)and 3a,12a,17a,20-tetrahydroxy-4amethylpregn-8-ene(2)and three new sesquiterpenoids,12-hydroxy-a-cadinol(3),3a,12-dihydroxy-d-cadinol(4),and 3a,6a-dihydroxyspiroax-4-ene(5),have been isolated from cultures of the fungus Phellinus igniarius.Their structures were characterized based on extensive spectroscopic data.In preliminary in vitro assays,compounds 3 and 4 exhibited the vascular-activities against phenylephrine-induced vasoconstriction with the relaxing rates of 11.0%and 7.0%at 3910-4 M,respectively.

Irpexoates A-D,Four Triterpenoids with Malonyl Modifications from the Fruiting Bodies of the Medicinal Fungus Irpex lacteus

Four eburicane-type triterpenoids with malonyl modifications,namely irpexoates A-D(1-4),were isolated from the fruiting bodies of the medicinal fungus Irpex lacteus.The structures of the new compounds were established by extensive spectroscopic methods,including 1D and 2D NMR,HRESIMS spectroscopic analysis.Irpexoate B(2)displayed weak cytotoxicity against four human cancer cell lines(A-549,SMMC-7721,MCF-7,SW480)with IC50 values varying from 22.9 to 34.0 pM,and irpexoate D(4)showed weak cytotoxicity against the human cancer cell line SW480 with an IC50 value of 35.2μM.

Structure-Based Optimization and Biological Evaluation of Pancreatic Lipase Inhibitors as Novel Potential Antiobesity Agents

The unusual fused b-lactone vibralactone was isolated from cultures of the basidiomycete Boreostereum vibrans and has been shown to significantly inhibit pancreatic lipase.In this study,a structure-based lead optimization of vibralactone resulted in three series of 104 analogs,among which compound C1 exhibited the most potent inhibition of pancreatic lipase,with an IC50 value of 14 nM.This activity is more than 3000-fold higher than that of vibralactone.The effect of compound C1 on obesity was investigated using high-fat diet(HFD)-induced C57BL/6 J obese mice.Treatment with compound C1 at a dose of 100 mg/kg significantly decreased HFD-induced obesity,primarily through the improvement of metabolic parameters,such as triglyceride levels.

New Diterpenes from Cultures of the Fungus Engleromyces goetzii and Their CETP Inhibitory Activity

One new cleistanthane-type diterpene named engleromycenolic acid A(1),one new rosane-type diterpene named engleromycenolic acid B(2)and one new natural rosane-type diterpene,engleromycenol(3),along with three known rosanetype diterpenes,rosololactone(4),rosenonolactone(5)and 7-deoxyrosenonolactone(6)were isolated from cultures of the fungus Engleromyces goetzii,where it naturally grows on Alpine bamboo culms.The new compounds were elucidated based on their spectroscopic data.In addition,compounds 1–6 were evaluated for their cholesterol ester transfer protein(CETP)inhibition activity.This paper reports the isolation,structural elucidation,and CETP inhibition activity of these compounds.

Isoprenylated flavonoids and clerodane diterpenoids from Dodonaea viscosa

Phytochemical investigation of the aerial parts of Dodonaea viscosa led to the isolation of six new compounds including four isoprenylated flavonoids,dodovisones A-D(1-4),and two clerodane diterpenoids,dodovislactones A and B(5 and 6).Their structures were established by extensive spectroscopic analysis.

Xylanilyticolides A-C,Three New Compounds from Cultures of the Actinomycete Promicromonospora xylanilytica YIM 61515

Three new lactones,xylanilyticolides A-C(1-3),were isolated from cultures of the actinomycete Promicromonospora xylanilytica YIM 61515.Their structures were elucidated by 1D and 2D NMR spectroscopic data in conjunction with HRESIMS analysis.Compound 1 exhibited potent cytotoxicities against five human cancer cell lines HL-60,A-549,SMMC-7721,MCF-7 and SW480 with the IC_(50) values of 3.9,15.2,11.2,5.9,and 4.7 pM,respectively.

Nine New Farnesylphenols from the Basidiomycete Albatrellus Caeruleoporus

Nine previously-unreported farnesylphenols,involving eight neogrifolin derivatives(1–8)and one grifolin analogue(9),together with three known compounds,were isolated from the fruiting bodies of the mushroom Albatrellus caeruleoporus.Their structures were elucidated as(S)-17-hydroxy-18,20-ene-neogrifolin(1),(S)-18,19-dihydroxyneogrifolin(2),(S)-9-hydroxy-10,22-ene-neogrifolin(3),(9S,10R)-6,10-epoxy-9-hydroxyneo grifolin(4),(9S,10R)-6,9-epoxy-10-hydroxyneogrifolin(5),(-)-13,14-dihydroxyneogrifolin(6),albatrelin G(7),albatrelin H(8),and one grifolin analogue,(S)-10-hydroxygrifolin(9),grifolin(10),neogrifolin(11),and albatrellin(12)by extensive spectroscopic analyses and chemical methods.Compounds 7 and 8 showed weak cytotoxic activity to cell lines HL-60,SMMC-7721,A-549,and MCF-7,in vitro.

Structures and cytotoxicities of three new sesquiterpenes from cultures of Armillaria sp.

Three new sesquiterpene aryl esters,named 10-dehydroxy-melleoliede B(1),1-O-formyl-10-dehydroxy-melleoliede B(2)and 10-oxo-melleoliede B(3)together with six known ones(4-9),were isolated from the cultures of Armillaria sp.The structures of the new compounds were elucidated based on the extensive spectroscopic methods.Compounds 1,2,and 5-9 exhibited moderate cytotoxicities.

Cyathane diterpenoids from fruiting bodies of Phellodon niger

Four new cyathane-type diterpenoids,nigernins C-F(1-4),together with four known compounds,were isolated from the fruiting bodies of the basidiomycete Phellodon niger.The structures of these new compounds were established on the basis of spectroscopic analysis,including 1D and 2D NMR experiments.In addition,nigernin F(4)with an unusual 3,4-seco cyathane diterpenoid skeleton was found to occur in nature for the first time.It was suggested to be as an oxidation product of C-3-C-4 bond cleavage of nigernin E(3).

Non-isoprenoid botryane sesquiterpenoids from basidiomycete Boletus edulis and their cytotoxic activity

Three non-isoprenoid botryane sesquiterpenoids,named boledulins A-C(1-3),have been isolated from the cultures of basidiomycete Boletus edulis Bull.The structures were established by means of spectroscopic methods.Boledulin A(1)exhibited moderate inhibitory activity against five human cancer cell lines.

Four New Sesquiterpenoids from Cultures of the Fungus Phellinidium sulphurascens

Four new sesquiterpenoids,namely 12-hydroxy-3-oxodrimenol(1),11-hydroxyacetoxydrim-7-en-3b-ol(2),2,6-dimethyl-7,10-epoxy-10-hydroxymethyldodeca-2,11-dien-6-ol(3),and 7,10-epoxy-2,6,10-trimethyldodeca-2,11-diene-4,6-diol(4),along with fourteen known compounds,were isolated from the cultures of Phellinidium sulphurascens.The structures of compounds 1–4 were established on the basis of extensive spectroscopic analysis.All of them were evaluated for their cytotoxic activities.