World Health Organisation (WHO) has defined medicinal plants as plants that
contain properties or compounds that can be use for therapeutic purposes or those
that synthesize metabolites to produce useful drugs (WHO 2008). Medicinal plants
constitute an important component of flora and are widely distributed in India. The
pharmacological evaluation of substances from plants is an established method for
the identification of lead compounds which can leads to the development of novel
and safe medicinal agents. The importance of medicinal plants and traditional health
systems in solving the health care problems of the world is gaining increasing
attention. Because of this resurgence of interest, the research on plants of medicinal
importance is growing phenomenally at the international level, often to the detriment
of natural habitats and mother populations in the countries of origin. Most of the
developing countries have adopted traditional medical practice as an integral part of
their culture. Historically, all medicinal preparations were derived from plants,
whether in the simple form of raw plant materials or in the refined form of crude
extracts, mixtures, etc. Recent estimates suggest that several thousands of plants
have been known with medicinal applications in various cultures.
A large proportion of such medicinal compounds have been discovered with the aid
of ethno-botanical knowledge of their traditional uses. The rich knowledge base of
countries like India and China in medicinal plants and health care has led to the keen
interest by pharmaceutical companies to use this knowledge as a resource for
research and development programs in the pursuit of discovering novel drugs. India
is a varietal emporium of medicinal plants and it is one of the richest countries in the
world as regards genetic resources of medicinal plants. It exhibits a wide range in
topography and climate, which has a bearing on its vegetation and floristic
composition. More over the agro climatical conditions are conducive for introducing
and domesticating new exotic plant varieties. At present majority of the people are
relying for their primary health care on traditional medicine.
The number of plants with medicinal properties far exceeds the number of plants
used as food source. For instance, Chinese herbalists have identified more than
5,000 medicinally important indigenous plants and the Amazon, the Golden triangle
region of northern Thailand, the tropics of the Venezuela-Guyana border, and the
teeming forests of central Africa, all have native human populations using
9
indigenous plant resources for healing purposes. However, despite the huge
biological potential of epiphytes and endophytes associated with these higher plants,
these microorganisms have received little attention. The search for bioactive natural
products of endophytic fungi, isolated from higher plants, are attracting considerable
attention from researchers worldwide, as indicated by the increase of work and
publications on therapeutic potential during recent years.
Since the discovery of the world’s first billion-dollar anticancer drug, paclitexel
(Taxol) from Pestalotiopsis microspora, a fungus that colonizes the Himalayan yew
tree Taxus wallichiana, without causing apparent injury to the host plant, interest is
growing in symptomless parasitic fungi, termed the ‘endophytes’. The term
endophyte is applied to fungi (or bacteria) which live within plant tissues, for all or
part of their life cycle and cause no apparent infections`.
Types of Endophytes
Fungal endophytes are categorized into two groups: Calvicipitaceous (Cendophytes) and Non Calvicipitaceous (NC-endophytes) based on their phylogeny
life history traits. C-endophytes represent small number of phylogenetically related
calvicipitaceous species and are limited to some cool and warm season grasses
(Bischoff and White 2005). Basically these endophytes occur within plant shoot and
rhizome, where they form systemic intercellular infections. Transmission of these
endophytes is primarily vertical with maternal plants passing fungi on to offspring
via seed infection (Saikkonen et. al. 2002). C-endophytes frequently increase
biomass, confer drought tolerance and produce chemicals that are toxic to animals
consequently decrease herbivory. However, the benefits conferred by these fungi
appear to be depending on the host species, host genotype and environmental
conditions (Saikkonen et. al. 1999; Faeth and Sullivan 2003; Faeth et. al. 2006). The
NC endophytes are further classified into three functional groups on the basis of
differences in life history, ecological interactions and other traits.
Group I: It comprises a diversity of species, all of which are members of the
Dikarya (ascomycota or basidiomycota). The group 1 NC endophytes are distinct
from other NC endophytes because they generally colonize roots, stems and leaves.
They are capable of forming extensive infection within plants; are transmitted via
seed coats/rhizomes, have low abundance in the rhizosphere; confer habitat adapted
10
fitness benefits in addition to non habitat adapted fitness benefits; and typically have
high infection frequencies (90-100%) in those plants growing in high stress habitats.
Group II: These NC endophytes colonize exclusively in above ground tissues;
transmitted horizontally, with formation of highly localized infections, the potential
to confer benefits or costs on host that are not necessarily habitat-specific; and
extremely high in plant biodiversity.
Group III (Dark Septate Endophytes): DSE are distinguished as functional groups
based on the presence of darkly melanized septa and their restriction to plant roots;
Horizontal transmission/ extensive colonization. These are primarily ascomycetous
that are conidial or sterile and that form melanized structures such as inter and
interacellular hyphae and microsclerotia in the roots. DSE have little host or habitat
specificity. They appear to be universal in occurrence and abundant across various
ecosystems. DSE may play an important role in the ecophysiology of plants.
3.1- Isolation of fungal endophytes from various tissues of host plants from
different Sites
Natural products still remains the most important source for the discovery of new
and potential drug molecules. Large number of plants, microbial and marine sources
has been tested for production of bioactive compounds. Number of natural products
with diverse chemical structures; have been isolated as pharmaceutical agents. An
increase in the number of people in the world, health problems caused by diseases
like cancers, diabetes, drug resistant bacteria, parasitic protozoans and fungi is a
cause for alarm. An intensive search to deal with these problems and endophytes are
a novel source of potentially useful medicinal compounds. Table 1 describes the
name of the most of the host plants and the number of fungal endophytes isolated
worldwide.
3.2- Seasonal fluctuations in fungal endophytes from different plants
Endophytic fungi have been isolated from leaves, stems and roots of woody plants in
the temperate regions and the tropics (Rodrigues 1994; Wilson and Carroll 1994;
Frohlich and Hyde 1999). Tropic plants are expected to support a high diversity of
endophyte (Lodge et. al. 1996) and only few of them have been screened for
endophytes presence (Rodrigues and Petrini 1997; Suryanaryanan et. al. 2001).
11
Endophytic fungi inhabiting the foliage of woody plants have been far less studied
than endophytes of grasses, although they are usually more diverse and abundant
than those in grasses (Petrini 1986).
Bills and Polishook (1991) isolated 659 fungal species from the bark of single
Carpinus carpiniana tree, which suggested the enormous extent of fungal diversity
associated within a single plant. Okane et. al. (1998) reported endophytic
assemblages in different leaf stages of eight species of Ericcaceae. Taylor et. al.
(1999) reported fungal endophytes associated with the palm Trachycarpus furtunei,
within and outside its natural geographic range. Endophytes were relatively common
with colonization rates 23-57% at the four sites sampled.
Rajagopal and Suryanaryanan (2000) isolated five endophytes from the leaves of
neem. Of these, four were sterile forms and one was Fusarium avenaceum. The
result showed that colonization frequency percentage of endophytes was
significantly higher in the monsoon season (49.6%) than during the dry seasons
(24.3%). Suryanaryanan and Rajagopal (2000) isolated 963 isolates belonging to 36
fungal species from the bark tissues of ten tropical forest trees. Of these, four were
Ascomycetes, one belonged to Coelomycetes and eleven were Hyphomycetes, rests
were sterile mycelial forms.
Ananda and Sridhar (2002) reported and isolated twenty seven different fungal taxa
and only 19 fungal endophytes were present in frequencies of colonization higher
than 1% from symptomless lamina and petiole of Acer saccharum. Suryanarayanan
et. al. (2002) studied tropical forests in Nilgiri Biosphere Reserve of the Western
Ghats for endophyte assemblages based on host recurrence and spatial heterogeneity
of their endophytes and concluded that dry tropical forests had much less
endophytes diversity as compared to wet tropical forests. Moreover, Gao et. al.
(2005) reported broad spectrum of endophytic fungi with Heterosmilax japonica in
China. The results also showed that the samples collected in spring harbored more
abundant endophytic populations in summer, implying seasonal fluctuations for
endophytes in H. Japonica.
Furthermore, Tejesvi et. al. (2006) isolated fungal endophytes from inner bark
segments of ethnopharmaceutically important medicinal tree species namely
Terminalia
arjuna,
Crataeva
magna,
12
Azadirachta
indica,
Holaarrhena
antidysenterica, Terminalia chebula and Butea monosperma growing in different
regions of Southern India and species of Fusarium, Pestalotiopsis, Myrothecium,
Trichoswema, Verticillium and Chaetomium were isolated.
In addition the study of Unterseher et. al. (2007) in temperate forest canopy also
suggested seasonal patterns associated with the fungal endophytes assemblages.
Similar seasonal and tissue age influences on endophytic fungi of Pinus
tabulaeformis (Pinaceae) were observed by Guo et. al. (2008) and many factors such
as sampling site, tissue effects were reported by Gonzlaez and Tello (2011).
3.3- Bioefficacy of fungal endophytes revealing antimicrobial, hypoglycemic,
hypolipidemic and antioxidant activities
Endophytes are a poorly investigated group of microorganisms that represent
secondary metabolites having an immense impact on modern medicine, since about
40% of prescription drugs are based on them. Endophytes contain different bioactive
compounds for commercial exploitation for vital therapeutic emergencies, which
mainly include alkaloids, benzopyranones, chinones, cytochalasines, depsipeptides,
enniatines, flavonoids, furandiones, isocumarines, peptides, polyketones, phenols,
quinols, terpenoids, tetralones and xanthones and have been reported to elicit a
number of pharmacological effects. Table 2 briefly summarizes fungal endophytes,
the host plant, different bioactive secondary metabolites produced and their
bioactivity.
3.4- Phytochemical screening from endophytic fungi extract
In 1960, a group of academic and industrial scientists at the Istiuto-Superiore di
Sanita in Rome described in a preliminary report (Arcamone et. al. 1960), followed
by a detailed one (Arcamone et. al. 1961), the production of ergot alkaloids in
submerged culture, with a strain of Claviceps paspali of reasonable yields (about
1000 ug/ml) of Lysergic acid hydroxyethylamide, a new simple Lysergic acid
derivatives. Alkaloids have been reported as a group of basic organic substances of
plant and microbial origin, containing at least one nitrogen atom in a ring structure
in the molecule.
The first microbial alkaloids to be recognized and studied were those of Claviceps
purpurea, the agent causing ergot of rye. These alkaloids can be isolated from the
13
sclerotia formed after infection of the ovaries of the plant by Claviceps ascospores
or conidia. Besides the sclerotia of Claviceps, other fungi and several higher plants
are known to contain, ergot alkaloids. Until 1960, however, no attempt had been
successful in obtaining more than trace amounts of alkaloids. In the same year some
other scientists isolated Lysergol, Lysergine and Lysergene. Koshino et. al. (1989)
have described compounds, toxic to some fungi, which include sesquiterpenes,
chokols, hydroxyl-unsaturated fats, phenolic glycerides and an aromatic sterol which
are produced in the mycelial-choked heads of timothy.
Yue et. al. (2000) have identified a number of compounds produced by cultures of
Epichloe and Neotyphodium species that have antifungal activity against the
chestnut blight fungus Cryphonectria parasitica and suggest that they may play a
similar role against other pathogens, the compounds in this study which showed the
greatest antifungal activity were the indole derivatives indole-3-acetic acid and
indole-3- ethanol, a sesquiterpene and a diacetamide. Furthermore, the production of
antimicrobial substances, such as antibiotics or HCN, is an important mechanism to
fight phytopathogens (Blumer and Haas 2000). Each of these antibiotics contains,
by virtue of their amino acid compositions, alanine, serine, and an unknown amino
acid. Colletotric acid, a metabolite of Colletotrichum gloeosporioides, an endophytic
fungus in Artemisia mongolica, displays antimicrobial activity against bacteria as
well as against the fungus Helminthosporium sativum (Zou et. al. 2000).
Endophyte effectively inhibits and kills certain other fungi and bacteria by
producing a mixture of volatile compounds (Strobel et. al. 2001). The majority of
these compounds have been identified by gas chromatography-mass spectrometry,
synthesized or acquired, and then ultimately made into an artificial mixture. This
mixture mimicked the antibiotic effects of the volatile compounds produced by the
fungus. The newly described Muscodor roseus was twice obtained from tree species
growing in the Northern Territory of Australia. This fungus is just as effective in
causing inhibition and death of test microbes in the laboratory as Muscodor albus
(Worapong et. al. 2002). Another endophytic streptomycete (NRRL 30566), from a
fern-leaved Grevillea tree (Grevillea pteridifolia) growing in the Northern Territory
of Australia, produces, in culture, novel antibiotics called kakadumycins (Castillo et.
al. 2003). Chemical studies have revealed that the resin contains various flavonoids
14
(Zeng et. al. 2004). In addition, endophytic actinomycetes may also affect plant
growth either by nutrient assimilation or enhanced secondary metabolites
(anthocyanin) synthesis (Hasegawa et. al. 2006).
Podophyllotoxin (PDT), a well-known aryltetralin lignan with potent anticancer,
antiviral,
antioxidant,
antibacterial,
immunostimulation
and
anti-rheumatic
properties, mainly occurs in genera of Diphylleia, Dysosma, Sabina (also called
Juniperus), and Sinopodophyllum (also called Podophyllum) (Yang et. al. 2003;
Zeng et. al. 2004; Guo et. al. 2004; Eryberger et. al. 2006; Puri et. al. 2006; Lu et.
al. 2006; Cao et. al. 2007; Kour et. al. 2008).
Another Colletotrichum sp., isolated from Artemisia annua, produces bioactive
metabolites that showed varied antimicrobial activity as well. Guo et. al. (1998) first
reported an endophytic fungus Alternaria sp. isolated from the phloem of
Catharanthus roseus that had the ability to produce vinblastine. Later, Zhang et. al.
(2000)successfully discovered an endophytic Fusarium oxysporum from the pholem
of C. roseus that could produce vincristine. Yang et. al. (2004) also found an
unidentified vincristine-producing endophytic fungus from the leaves of C. roseus.
These results indicate that some endophytic fungi could be a potential source to
produce either vinblastine or vincristine.
Camptothecin (CPT), a pentacyclic quinoline alkaloid, was firstly isolated from the
wood of Camptotheca acuminate (Nyssaceae) by Wall et. al. (1966). CPT and its
analogue10-hydroxycamptothecin have been regarded as two of the most effective
antineoplastic agents. Vinblastine and vincristine, the terpenoid indole alkaloids
derived from the coupling of vindoline and catharanthine monomers, are two of the
well-known anticancer agents (Prez et. al. 2002; Wang et. al. 2010). The primary
action mechanism of vincristine is via interference with microtubule formation and
mitotic spindle dynamics, disruption of intracellular transport and decreased tumour
blood flow, with the latter probably as a consequence of anti-angiogenesis (Prez et.
al. 2002; Wang et. al. 2010; Moore and Pinkerton 2009). The antioxidant potential
may be directly linked to the phenolic compounds present in the endophytes,
Aspergillus niger and Fusarium oxysporum of Crotalaria pallida. The outcome of
the Govindappa et. al. (2011) investigation clearly indicates that A. niger and F.
oxysporum showed potential phytochemicals and they can used as antioxidants.
15
Table 1- List of endophytic mycobiota isolated worldwide from various host plants.
Host plant
Plant part
Nyctanthes arbortristis
Leaves and stem
Vitis vinifera
No. of
species
Location
Reference
19
India
Gond et. al.
(2011)
Leaves and shoot
68
Madrid
region
Central Spain
Gonzalez and
Tello (2011)
Paeonia delavayi
Root, stem and
leaves
19
China
Miao et. al.
(2011)
Panax
quinquefolium
Stems and roots
27
China
Xing et. al.
(2010)
Pecteilis susannae
Roots
8
Thailand
Chutima et. al.
(2010)
Holcus lanatus
Leaves and roots
134
Spain
Marquez et.
al. (2010)
Orchidaceae
Leaves, root and
stem
54
Brazil
Vaz et. al.
(2009)
Lamiaceae
Leaves
103
India
Banerjee et.
al. (2009)
Catharanthus
roseus
Leaves, root and
stem
13
India
Kharwar et. al.
(2008)
Allamanda
cathartica
Leaves roots stems
flower and
inflorescence
35
China
Huang et. al.
(2008)
Alstonia scholaris
Leaves roots stems
flower and
inflorescence
33
China
Huang et. al.
(2008)
Alyxia sinensis
Leaves roots stems
flower and
inflorescence
31
China
Huang et. al.
(2008)
Artemesia
capillaris
Leaves roots stems
flower and
inflorescense
42
China
Huang et. al.
(2008)
16
Artemesia indica
Leaves roots stems
flower and
inflorescense
39
China
Huang et. al.
(2008)
Artemesia
lactiflora
Leaves roots stems
flower and
inflorescense
27
China
Huang et. al.
(2008)
Cerbera manghas
Leaves roots stems
flower and
inflorescence
44
China
Huang et. al.
(2008)
Cestrum naturnum
Leaves roots stems
flower and
inflorescence
40
China
Huang et. al.
(2008)
Dischidia
chinensis
Leaves roots stems
flower and
inflorescence
34
China
Huang et. al.
(2008)
Graphistemma
pictum
Leaves, roots,
stems, flower and
inflorescence
33
China
Huang et. al.
(2008)
Gymnema
sylvestre
Leaves, roots,
stems, flower and
inflorescence
38
China
Huang et. al.
(2008)
Hoya carnosa
Leaves, roots,
stems, flower and
inflorescence
29
China
Huang et. al.
(2008)
Melodinus
suaveolens
Leaves, roots,
stems, flower and
inflorescence
42
China
Huang et. al.
(2008)
Nerium oleander
Leaves, roots,
stems, flower and
inflorescence
42
China
Huang et. al.
(2008)
Pavetta
hongkongenesis
Leaves roots stems
flower and
inflorescence
23
China
Huang et. al.
(2008)
Polygonum
capitatum
Leaves, roots,
stems, flower and
inflorescence
48
China
Huang et. al.
(2008)
17
Polygonum
chinense
Leaves, roots,
stems, flower and
inflorescence
41
China
Huang et. al.
(2008)
Polygonum
cuspidatum
Leaves, roots,
stems, flower and
inflorescence
46
China
Huang et. al.
(2008)
Polygonum
multiforum
Leaves, roots,
stems, flower and
inflorescence
35
China
Huang et. al.
(2008)
Scutellaria indica
Leaves, roots,
stems, flower and
inflorescence
33
China
Huang et. al.
(2008)
Strophanthus
divaricata
Leaves, roots,
stems, flower and
inflorescence
70
China
Huang et. al.
(2008)
Tabernaemontana
divaricata
Leaves, roots,
stems, flower and
inflorescence
83
China
Huang et. al.
(2008)
Thevetia pervuiana Leaves, roots,
stems, flower and
inflorescence
36
China
Huang et. al.
(2008)
Toxocarpus
wightianus
Leaves, roots,
stems, flower and
inflorescence
43
China
Huang et. al.
(2008)
Trachelospermum
jasminoides
Leaves ,roots,
stems, flower and
inflorescence
43
China
Huang et. al.
(2008)
Tylophora ovata
Leaves, roots,
stems, flower and
inflorescence
43
China
Huang et. al.
(2008)
Pinus
tabulaeformis
Needle and
branches
24
Beijing
Guo et. al.
(2008)
8
Pakistan
Rezwana et.
al. (2007)
34
Korea
Paul et. al.
(2007)
Calotropis procera Leaves, stem
Aralia species
Roots
18
Dipodium
variegatum
Roots
5
Australia
Dearnaley
(2006)
D.
Roots
3
Australia
Dearnaley
(2006)
Roots
6
Australia
Dearnaley
(2006)
Callicarpa
tomentosa
Bark, stem and
leaves
11
Western
Ghat, India
Raviraja
(2005)
Lobelia
nicotnifolia
Bark, stem and
leaves
5
Western
Ghat, India
Raviraja
(2005)
Plumeria rubra
Leaves
21
India
Suryanaryanan
and
Thennarasan
(2004)
Cordemoya
integrifolia
Leaves
27
Mauritius
Toofanee and
Dulymamode
(2002)
Acer saccharum
Lamina and petiole
27
India
Ananda and
Sridhar (2002)
28
India
Suryanaryanan
and
Vijaykrishna
(2001)
hamiltonianum
Erythrorchis
cassythoides
Ficus benghalensis Leaf and aerial
tissues
Lycopersicon
esculentum
Leaves
15
Argentina
Larran et. al.
(2001)
Cuscuta reflexa
Stems
45
India
Suryanaryanan
et. al. (2000)
Azadirachta indica
Leaves
5
India
Rajagopal and
Suryanaryanan
(2000)
19
Table 2- Overview of some important endophytic secondary metabolites with
antimicrobial, anticancerous, antioxidant and antidiabetic activities.
Fungal
Host plant
endophyte
Unidentified
Compound
Activity
Reference
Antibacterial and
Qin et. al.
antifungal against
(2011)
isolated
Arbutus unedo
Anofinic acid
ascomycete
Eschrichia coli,
Bacillus megaterium,
Microbotryum
violaceum
Nigrospora
oryzae
Nyctanthes
arbor- tristis
Bioactive extract
Gond et. al.
(2011)
Phenylpropanoid
Antibacterial activity
against Shigella sp.
And Pseudomonas
aeruginosa
Antimicrobial
activity against an
array of Pathogenic
fungi and bacteria
Anticancer,
A. niger, A.
alternata
Tabebuia
argentea
Naphthaquinone
Penicillium
Melia
brasililianum
azedarach
amides
antioxidant,
(2010)
antimicrobial,
anti
inflammatory
and
Sadananda
et. al. (2011)
Fill et. al.
immunosuppressive
agent
Nodulisporium
Erica arborea
sp.
Aspergillus
Juniperus
fumigatus
communis
Phomopsis sp.
Laurus azorica
Nodulisporins
D Antibacterial
And Dai et. al.
and F
Antifungal
(2009)
Podophyllotoxin
Potent anticancerous Kusari et. al.
activity
(2009)
Cycloepoxytriol B Antibacterial
and
antifungal
Cycloepoxylactone against
and Hussain
activity al. (2009)
Bacillus
megaterium
Microbotryum
violaceum
20
and
et.
Alternaria
Compound
Cytotoxic
isolated
towards HeLa cells
Rehmannia
2,6-Dihydroxy-2-
Active
glutinosa
methyl-7-(prop-1
Verticillium sp.
(2009)
7-amino-4-
Antibacterial and
Liu et. al.
methylcoumarin
antifungal activity
(2008)
Coffea arabica
alternata
Verticillium sp.
activity Fernandes
et. al. (2009)
against You et. al.
E-enyl)-1benzofuran-3(2H)one
Xylaria sp.
Ginko biloba
against
Staphylococcus
aureus, E. coli,
Salmonella typhi, S.
typhimurium, S.
enteritidis,
Aspergillus
hydrophila, Yersinia
sp., Verticillium
albicans, A. niger
Ampelomyces
Urospermum
6-O-
antimicrobial activity
Aly et. al.
sp.
picroides
methylalaternin
against gram positive
(2008)
and altersolanol
pathogens,
Staphylococus
aureus, S.
epidermidis,
Enterococcus
faeccalis
Phomopsis sp.
Mangrove
Cytosporone
and C
B Antifungal
against
albicans
activity Huang et. al.
Candida (2008)
and
Fusarium oxysporum
21
Cladosporium
Quercus viriabilis Brefeldin A
antibiotic
Wang et. al.
(2007)
sp.
Muscodor albus
Tropical tree
Tetrohydofuran, 2- Active
against Atmosukarto
methyl furan, 2- Stachybotrys
butanone,
et. al. (2005)
chartarum
aciphyllene
Phomopsis
Cassia spectabilis Ethyl
cassiae
2,4- Antifungal
activity Silva et. al.
dihydroxy-5,6-
against
two (2005)
dimethylbenzoate
phytopathogenic
and
fungi Cladosporium
phomopsilactone
cladosporioides and
C. sphaerospermum
Xylaria sp.
Abies halophylla
Griseofulvin
Antibiotic agent used Park et. al.
against the treatment (2005)
F0010
of human mycotic
diseases
Penicillium
Melia
janthinellum
azedarach
Citrinin
100%
antibacterial Marinho et.
activity
against al. (2005)
Leishmania sp.
Cephalosporium Trachelospermum Graphislactone A
Free
sp. IFB-E001
scavenging
radical Song et. al.
and (2005)
antioxidant activities
Acremonium
Maize
Pyrrocidines A, B
Zeae.
Active
against Wicklow et.
Aspergillus
al. (2005)
flavus,Fusarium
verticillioides
Aspergillus
Cyndon dactylon
Asperfumoid,
Inhibit C. albicans
fumigatus
Fumigaclavin
C,
CY018
Fumitremorgin C,
Physcion, Helvoic
acid
22
Liu et. al.
(2004)
Aspergillus
Cynodon
Rubrofusarin
niger IBF-E003
dactylon
Aurasperone A
B, strong co inhibitors Song et. al.
on xantin oxidase , (2004)
colon cancer cell and
some
microbial
pathogens
Antibiotic
activity, Weber et. al.
Medicago
initiation
of (2004)
lupulina
apoptosis in cancer
Phoma
Medicago sativa,
medicaginis
Brefelidine A
cells
Phomopsis sp.
Erythrina
Mevinic acid
Anti-inflammatory
Weber et. al.
activity
(2004)
and Antioxidant,
Harper
cristagalli
Pestalotiopsis
Terminalia
Pestacin
microspora
morobenesis
isopestacin
antimycotic
et.
and al. (2003);
antifungal activity
Strobel
et.
al. (2002)
Curvularia
Niphates olemda
Cytoskrins
Antibacterial
activity,
lunata
Brady et. al.
potential (2000);
anticancer agent
Jadulco
et.
al. (2002)
Curvularia
Niphates olemda
Lunatin
Active
lunata
Bacillus
against Jadulco
et.
subtilis, al. (2002)
Escherichia
coli,
Staphylococcus
aureus,Cladosporium
herbarum
Pestalotiopsis
Torreya taxifolia
Torreyanic acid
Antifungal agent
Liu et. al.
(2001)
microspore
Monochaetia sp.
Rhinocladiella
Tripterygium
22-oxa-[12]-
sp.
wilfordii
Cytochalasin
23
Antitumour
Wagenaar
et. al. (2000)
Cytonaema sp.
Cytonic
Quercus sp.
acid
and B
A Human
Guo et. al.
cytomegalovirus
protease
(2000)
inhibitor
(HCMV)
Pseudomassaria From
sp.
African Nonpeptidal
rainforest
Insulin
near fungal metabolite compound
Kinshasha in the (L-783,281)
Democratic
Republic of the
Congo
24
mimetic Zhang et al.
(1999)