natural products form plants
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MEDC 603 Fall 2007 1
Presented By
G.SUBHASRI
14UBCH040
II-BIO CHEMISTRY
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MEDC 603 Fall 2007 2
Natural products evolved for self-defense!!
Amazing are the natural products that apparently evolved
only for the purpose of alleviating our diseases, e.g., the
statins
Traditionally natural products are plant products, e.g.,
morphine from Papaver somniferum or digitoxin fromDigitalis
Plants form the bul of natural product suppliers current
estimate of number of plant species on earth is " million
These days natural products are obtained from plants, algae,
insects, bacteria, yeast, animals, .
Natural Products
General
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MEDC 603 Fall 2007 3
• Evolution against challenges
• #tructural diversity
• $Apparently% unlimited &uantity
• Potency
Natural Products
Advantages of Natural Products
Disadvantages of Natural Products
• #ynthesis
• 'solation
• 'dentification
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MEDC 603 Fall 2007 4
Natural Products
Typically process of drug discovery from naturalsources• Pre-knowledge helpful (cultural folklore, Chinese
Materia Medica, Indian Ayurveda, ….)
• (ollect source (plant, algae, animals, ….)
• #creen extracts (organic + aqueous extractions)
•)'T!!
• (hromatographic separation
• #creen individual components
• )'T or *'##++
• #tructural identification
• 'ndependent synthesis and re-bioassay
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MEDC 603 Fall 2007 5
Natural Products
Selected Examples of Natural Product derivedDrugs
CH3
CH3
O
O
OH
H
H
HOOOHO
OH
H3C
H3C
OH H3C
OH
CH3
CH3
O
O
OH
H
H
HOOOHO
OH
H3C
H3C
OH H3C
OH
OHDigitoxin
Digoxin
Digitalis purpurea (Foxglove) and Digitalis lanata … long known for their healthy heart
effects … exert a positive inotropic effect on cardiac muscles … treatment for heart
failure
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MEDC 603 Fall 2007 6
Natural Products
Selected Examples of Natural Product derivedDrugs
N
N
HOH
OCH3
H N
N
OCH3
H
H
OH
Quinidine Quinine
Quinidine …bark of Cinchona tree …… anti-arrhythmic drug
Quinine … no cardiac activity … anti-infective … malaria
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NH
N
H H
H
MeOOC
OCH3
O
OOCH3
OCH3OCH3
MeO
Reserpine
Natural Products
Selected Examples of Natural Product derivedDrugs
Reserpine …… alkaloid from Rauwolfia serpentina plant … lead from the Indian
yurvedic system as good for heart !!! used as anti-hypertensive … the plant was a
source of "#$ different alkaloids …
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Natural Products
Selected Examples of Natural Product derivedDrugs
…… fungal metabolites !!! first fungal metabolite was compactin which inhibited %&'-
o reductase … compactin is isolated from Penicillium citrinum Penicillium
brevicompactin and Penicillium cyclopium ..! an anti-fungal agent too but toxic !!!
()-
.
,-.()- (-
,)
,()-()-
Meastatin R!"R#"H$oastatin R!"H% R#"CH3&imastainR!"R#"CH3 'raastatin
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Natural Products
Selected Examples of Natural Product derivedDrugs
*icoumarol … … coumarin derivative … coumarin is widely distributed in nature … high
concentrations in tonka beans (Dipteryx odorata) and also in Melitotus albus (sweet
clover) … a hemorrhagic disorder was observed in animals that had consumed spoiled
stuff composed of sweet clover …
O O
OH
CH3
O
O O
OH
OO
OH
(
arfarin !icou"arol
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Natural Products
Selected Examples of Natural Product derivedDrugs
Heparin … trying to find a coagulant !!! accidentally found an anticoagulant+ …
structure took decades to come about … now we have low molecular weight heparin
and heparin pentasaccharide …
O
OH
OH
O
COO
O
O
CH#OH
NH&O3
OH
O
O
CH#O&O
3
NH&O3
OH
O
OH
OH
O
COOO
O
CH#O&O
3
NH&O3
OH
O
O&O3
OH
O
COOO
O
CH#O&O
3
NHCOCH3
OH
)
)
)
)
)
)
)
) )
)
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Natural Products
Overview of Natural Products as Drugs Status inthe Period !"#$%%$
0
100
200
-00
300
400
5 6 NP NP7 #NP #
* " a++ines
" -iologi+alsN' " natural produ+ts
N'D " natural produ+t deriaties
&N' " snt/eti+s deried 0rom N'
& " straig/t snt/eti+s
Co"#iled fro" $
%e&"an, !. '., Cragg, . M., and nader, *. M. (-) %A/0A1 203!/C A 3/0C4 35
%4 !0/ 3640 74 240I3! 89:8 ; . 'ournal of %atural 2roducts 88, 8
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Natural Products
Structural &omparison 'etween Natural Productsand &om'inatorial &ompounds
Combn!tor!" Com#o$nds
%!t$r!" Prod$&ts
'r$(s
Data from Feher and Schmidt, J. Chem.Inf. Comput. Sci (2003) (), 218.
Statistica! de"ned chemica space issimiar for natura products and dru#s,$hie com%inatoria compounds anddru#s do not share simiar space.
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Natural Products
&urrent E*orts
()-
()-
,)
,)
)
()-
) ()-
Trinervitane derivative
Nasute termites &. Sodier termites
use their no''e (suirt #un) to tan#eup the inader in their to*ic #ue &.%ein# deeoped %! +ntocosm, ustraiaas an anti%iotic &. the natura productis 10 times ess potent than a cinica!
practica anti%iotic &. a potent -ead
moecue
#
N
,,
()-
,
,)
,)
*e
()-
()-
()-
*e *e
9pothilone 7
/ri#ina! identi"ed throu#h s!nthesis& epoD $as found to %e produced %!certain %acteria & #enetic en#ineerin#& po!etide s!nthase #ene nocout
(epoD to epo) & #ood !ieds & %ein#deeoped %! osan, C as an antitumor(inhi%ition of microtu%ue formation)
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ANTICANCER AND ANTI-HIV DRUGS DERIVED FROM
AFRICAN AND OTHER PLANTS
Gordon Cragg, Ph.D.
NIH Spe!a" Vo"#n$eer
Na$#ra" Prod#$% &ranh
De'e"op(en$a" Therape#$!% Progra(
D!'!%!on o) Caner Trea$(en$ and
D!agno%!%
NCI-Freder!*
Fa!r'!e+ Cen$er, S#!$e
P. O. &o/ &
Freder!*, MD 01-00, U. S. A.
Phone2 30-45-63417 )a/2 30-45-014
e-(a!"2 raggg8(a!".n!h.go'
+e9%!$e2 h$$p2::d$p.n!.n!h.go'7h$$p2::d$p.n!.n!h.go':9ranhe%:np9:!nde/.h$("
mailto:craggg@mail.nih.govhttp://dtp.nci.nih.gov/http://dtp.nci.nih.gov/branches/npb/index.htmlhttp://dtp.nci.nih.gov/branches/npb/index.htmlhttp://dtp.nci.nih.gov/mailto:craggg@mail.nih.gov
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Traditional Medicine and
Drug Discover!
" 80# o$ t%e &orld 'o'ulation resides in develo'ingcountries
" 80# o$ 'eo'le in develo'ing countries utili(e 'lants
to )eet t%eir 'ri)ar %ealt% care needs" *lo+al 'o', ca, 6,3 +illion
- ca, 4 +illion 'eo'le utili(e 'lants to )eett%eir 'ri)ar %ealt% care needs
!Farns&ort% ./ et al, Medicinal lants in T%era', Bull. W.H.O. 63965981
0;46
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" Ana"ge%!%2 A%p!r!n2 Salix %pe!e%:E#rope
Morph!ne, Code!ne7 Papaver somniferum:
Me%opo$a(!a
" Card!o$on!2 D!g!$a"!n2 Digitalis purpurea:U?-
E#rope
" Ma"ar!a2 @#!n!ne2 Cinchona %pp.:A(aon!a
Ar$e(%!n!n2 Artemisia annua:Ch!na
" An$!hBper$en%!'e2 Re%erp!ne2 Rauwolfia
serpentina/ Ind!a
" Me(orB enhane(en$2 PhB%o%$!g(!ne2 Physostigma
venenosum:e%$ A)r!a
M#%"e re"a/an$2 T#9o#rar!ne2Chondrodendron %pp.:
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E'ot%ilone doced in tu+ulin active site
O
O
HO
O OOH
N
&
1
!! !3
!2
E'ot%ilone
solated $ro) gliding
+acteria
Mo+acteria
NATURE THE SUPREME MOLECULAR ARCHITECT
Ne$$"e% e$ a"., The &!nd!ng Mode o) Epo$h!"one A on a,-T#9#"!n 9B E"e$ron CrB%$a""ographB
S!ene, A#g#%$ 5, Vo". 36, pp. 4-4;
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PLANT-DERIVED ANTICANCER DRUGS
IN CLINICAL USE OR DEVELOPMENT
" V!n9"a%$!ne:V!nr!%$!ne2 Catharanthus roseus:a(a!a, Ph!"!pp!ne%
" E$opo%!de2 Podophyllum species: Ea%$ern US,
H!(a"aBa%
" Pa"!$a/e":Doe$a/e"2 Taxus %pe!e%:N US, E#rope
" Topo$ean:Ir!no$ean2 Camptotheca acuminata:Ch!na
" Ho(oharr!ng$on!ne2 Cephalotaxus
harringtonia:Ch!na
" F"a'op!r!do"2 SBn$he$! 9a%ed on roh#$!*!ne )ro( Dysoxylum binectariferum:Ind!a
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" 1987 Collected liana Ancistrocladus korupensis leaves,
:oru' .ational ar Munde)+a ;, *ereau .ovon 1993 3 494498,
" 1989 Mic%ella)ine = isolated, ctive against a range o$ ?@1
and ?@2 strains =od et al, A, Med, C%e) 1994 37 174045,
" ;u$$icient isolated $ro) $allen leaves $or 'reclinical develo')ent,
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MEDC 603 Fall 2007 20
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