Natural Products Form Plants

8/19/2019 Natural Products Form Plants

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MEDC 603 Fall 2007 1

Presented By

G.SUBHASRI

14UBCH040

II-BIO CHEMISTRY


2/20


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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• Evolution against challenges

• #tructural diversity

• $Apparently% unlimited &uantity

• Potency

Natural Products

Advantages of Natural Products

Disadvantages of Natural Products

• #ynthesis

• 'solation

• 'dentification


4/20


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


5/20


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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Natural Products


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


7/20MEDC 603 Fall 2007 7

NH

N

H H

H

MeOOC

OCH3

O

OOCH3

OCH3OCH3

MeO

Reserpine

Natural Products


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 …


8/20MEDC 603 Fall 2007 8

Natural Products


…… 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


9/20MEDC 603 Fall 2007 9

Natural Products


*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


10/20MEDC 603 Fall 2007 10

Natural Products


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

)

)

)

)

)

)

)

) )

)


11/20MEDC 603 Fall 2007 11

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


12/20MEDC 603 Fall 2007 12

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.


13/20MEDC 603 Fall 2007 13

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)


14/20

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:[email protected]://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:[email protected]


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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


16/20

" 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.:


17/20

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

Documents

Natural Products Form Plants