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iurn ums , ')fUl'I~l'I1fJFlHllJ'UfJ1ft~'U1~lft

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Noble Im:;flW:;(1949) '~'j1t1~1'UF-l"fll'j'YI~,,~~~11'j:;1'YIffU

fI'U'U1fl1 tYl'i ,,:; " 1t1l1l'1~l'I1t1'
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tYfl'f\ l'f\'\llflU 'I~'I1UfiHI'U1'Y11~'I1
ft8'f\tft 8'f\'f\1 fl tYll.1TH\ ft'f\1J'j l.Il\U l'l.I'fI
Ift~~'U11UCl:;fl~fllnh~l'U

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11
":;~ij1lll'l1J'hij"fl1"~tI~

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'Jj'ii~ii tY111l'iflfl 1" 1fJ

dd"'l

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ICIf""lI:;IH ')f'U~P1534 'U'I1'Ufl1J",m

qs~llJlJ~1'Y11
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Tu iftBllft:;ti1il1tiflUF-lft~ ''U~~~'I1~~~lmilJ~
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vincristine CIf~'U1J~~1J'UllJ'UfJl'lf'Ufl'l1'U~'YI
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vincristine lI11'YI1ifl~tYlIij\l

'lfii~d"h

vinblastine ~~~~1Ili~iiflln;9lJ'Ull'Y1f1

~'!1

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ci

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sulfate,

vincristine

.et

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sulfate,VCR,Oncovin 111I11'Y1\1
2 ')f'U~'U~:;1IflHtY'jH'YI1~lfllI'YIflft1t1f1ft~fllJU~lIf1111111~fl~1~fllJ
~fh~1Ilfl ''U~1'UtYnl'lflw''Ufll'j1fl1:l1
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n

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fl~ 11":;hflll:;1 ~~

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vinblastine Im:; vincristine CIf\l'~''Ufln1fl1:l1 hflll:;I~~

. ')fllJ'Utl1ft~fl1111~'U ift'l1~
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fll'j'~~lfJl~~mill

1.oe!l

ajrnalacine
..et

Cl

1I":;lii~~ijfl

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uenu muueu

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derivatives 'Uf)\If)ftfllftf)tI~'YI')f1t1'Cl~'.n~nft 'Umf)~l'lf'U l~tI'1fl1J 'UU'C'ftYl'1:;

'11
'j f)

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fJ1m-ll

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ffl1 l1fft1U

"hi'u ri Catharanthine,

leurosine,

vindolinine

IH1:;

dihydrovindolininel1lu~u

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8t'1flUU)fJVI

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1111..1
flftlJffl';i~iii'U
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flWfflJlr~11I'U~ 1~ 1I1flflWfflJlr~j'"J11lJliJ'U~ Hu'Yi11'lflllff11111tl fffl~Oftft1ft8 t1~1I1fl.w'lf
ill' ~t1fll1
1'If'Yi
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1ft6t1~~iiflW fflJlr~ft~ft1t1J 1i;; tl~ 11~ 11ff11 erft
mft6t1~1f{lltl'lfii~1I~ii-W1l (I'lf'Ustrychnine 1f16 coniine) lI~erftj'"J1ft6t1~111~~1n\lfl1~llIUfJ111ti'
tJ1~

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11J'U6~j'"JlJ1~fl611I'lfUpyrrolidine alkaloids 1flllfJtl.:j6ftmft6fJ~'fIlJ pyrrolidine ring

'lu 1~1111U
11..1,-llJlftf}ft

quinoline alkaloids 1flllfJtl.:jerftj'"J1ft6t1~~ii quinoline nng 1'U1111ftf}ft 1f18 indole alkaloids

.d/

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'YIlIltltl{j8ftj'"Jlm}tl~'fI1I
indole ring !u !lImfl{ll1JU~\\l
fllmt.i~tJ1~1fl'fl'll8.:jerftj'"Jlft6t1~~llJ1j'"J1.:jff1'1~
- pyridine group 1'lf'Upiperine, coniine, trigonelline, arecaidine, guvacine, pilocarpine,
cytisine, nicotine, sparteine
- tropine group 1'lf'Uatropine, cocaine, hygrine, ecgonine, pelletierine
- quinoline group l'lfU quinine, strychnine, brucine, veratrine, cevadine
- isoquinoline group 1'lf'Umorphine, codeine, thebaine, papaverine, narcotine
- phenethylamine group l'lfU methamphetamine, mescaline, ephedrine
- indole group 1'lf'Utryptamine

"

111~j'"J1~nllt.i~~llJ
1j'"JHff1'1~iiI1lu monocyclic, dicyclic,

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'U6fllllflU61lliifll';iIlt.i~tJ1~Ul'fl~llJmilJ'll8~.w'lfiiiierftj'"Jlft8t1~,:r'U'1I'lfU cinchona alkaloids

~

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1fllltltl~8ftj'"Jlft6t1~'fI'W111..1 Cinchona spp. Salonum alkaloids 1fllltltl~6,Unft8tJ~'fI'W11 U'W'lf1~ff

lJ~I.u6 (Solanaceae),
roseus, Aponaceae)

vinca alkaloids 'YIlllfJtl.:jerftj'"Jlft8t1~~'W11

11..111 'W~'W1
fJ~t.:l (Catharanthus
"
~
11Iu~u 1f16 1U111~fl1.:I81~~:;IIt.i.:ltJ1~!fl'fl~llJq'fli'fll'Hfl ff'lf1'f1t111'lf'U

mydriatic

i~lIt1 atropine,

alkaloids

"

protoveratrine ffl1 ~'1~ulhh~ty

hyoscine

Iu m:aJ1U

,111..1

hypotensive

alkaloids

l'lfU reserpine,

fll".i~1ff '11j'"Jn:;,f'll'f)'IOrlmrl6n~' ~Ut1 m ~'f):;ii1 'U

erftj'"Jlft6fJ~~ii1j'"JHff1'H1f~fllll1l1flfl1~6~ii1 'Ullft~iii'U 1~1111u6~1 'U heterocyclic ring 11fJfl11

true alkaloid

ff'H..!BiHilftf)f.f~~ijl
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f'lHfff HlfftmJ

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heterocyclic ring !HJfl11 protoalkaloid f)Ul.:JA'ifl~lll f)ftf'lll1f)U~tll.:J'lfU~ AllA~\lflff'iHlInlfl

fl'i~f)~ijl
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AflHff'il.:Jlfl1fl1IJ'Uffl'i1'41fl terpenoids 11'if) steroids Ul11Ifl~fll'iI~1I1\!1'41~ A'Ut~'iHI'U'illflflHI

'lu l~'i!'il'U~'UG"J'~lij'Ufflnh~flf)tl~ij''U

f)~ijl'U 'il1flfflnh~flf)tl

1~'i1'il'U''U 111!l1fll1ffl'ifl~lIif

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,
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metabolite ~l'lfl'U '1tJl'U~'U '1ll~l'1'lfU~fl'U lf18~1'1Q~flll1

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'1li't1'iltllllii'~
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mevalonate <1l1<1l~rJlIlf)'U A'lI'1I1'\J11llIflrJ1'\Jf)~'lI''1

-W'lf~l.:J'lfU~fl'U
'iI~ijI8'U'1'l1'lf~l'lfl'U fll "H1~'t1H
nd

'U1'4'lfffl'i 2
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l'ill~'UIIJ'Ufl'j~f)~lI ru (amino acid) ,acetate,

'1tJ ~'1'th il1'~ffl';j

i ~

.d

(secondary) metabolite nnu

mu ij

nu '1V>11'U-W'lfi''U
ff'llij'Uff1'U1I1fl lI~tll'lfli' 'In1'4tl'1V>11'UiY~111l1~
1'U'11
ft'U't116 Bl1f11l1f)U~ff';l'U
1

."

(organic solvent) 'lfU~~l'lG"J ijQfli

1ff'\J1I '1lil1~l1lrJth U~l1~l1lrJ'1~iU1'41fl~Trilft~l1lrJiju't116

!ij 'U~H

ff1 'U'l l1ili 'iI~lij 'U'\Jf)'111~'I i 'U~tJ

Nil n (crystalline

solid) tlH'lfU ~ lij 'U8 iYw!1'U

.
"
(amorphous) 1!l1~ijri1'Uil8rJi1I~'U'\Jtl.:Jmft1f1ft'lrJlhJj'U i1'b"t'Jfl'lfiifl'1i~1!~'U~8'1ij~ftfllftf)U~ !-M'U
" .
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1'U-W'lf1
tll~fN!~rJ1 Jjfl'il~'1lifi8fJii 1'U-W'lfi1iiBftfllftf)U~81'il1'4tlBftfllft8Ufl1~ 'Uri1'U~1'lG"J'\Jf)'1-W'lf

I-M'U1'U
11I~~ (lf1l1fl) 1'U~m(1'41fl'1't1tJ)'lu'ln (belladonna) i'UltJ~8fl

'lurin (aconite)

(cinchona) 1'U1lf~1 (ipecac)

lij'U~'U

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'ilU'U-Uij';jltJ'Il'U fll';j

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'lfU~ II~ Bftfllftf) tJ~~ i' flln hfl '1~ I~'U

vinblastine, vincristine 1Il1~ ajmalicine iif)~i'UtJ111lW~1 fll';jNft~ ajamalicine 91'1ij8~'ll'8tJ i'U.w'lf

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lIfl'il~ A~'iI1flfll';jff'llfl';jl~11'i11fl serpentine 'lI''1l1lJ';j1llW~'1 'U1'4'lf(Bombardelli , 1977) fll';jNl1~

vinblastine nffllll'Hl'th'1~'iI1flfll';jiY'IlfI'il~,f

l~fJ1~ anhydrovinblastine 'H18 Catharanthine 1Il1~

"

vindoline lij'Uffl1~"~'U (Endo, 1Il1~f1W~,1987; Mclauchlan Ul1~f1W~ 1983 ; Kutney Ul1~f1W~ ,

1976 Ul1~ Langlois Ul1~f1W~,1976) fll';jNil~ vincristine {VCR} nff11llHI'th'1~'iI1flfll';jiY"lfI'il~,f

dimeric

1~tJ'~ffl'~ffilfl1h'U1\ij
~

alkaloids ~1'U1'UlIlfl1l1'Yllf)1'j
QI'

formylation

.c::t...:t

Vegyeszeti, 1975 'H'jf)fll';j'Ul!81iY1H1'fl~ff1'U't111 N-demethylvinblastine

{Richter U~~

urmmr formylation

9
1~HJ1'l5
formic
j.I

1~tlfll11'l5

J'd
<V
1982) 'l.Hlfl'illfl'Wflbl'llJl1flbl':Wrl'n:;;'VI

acid U(;1:;;acetic anhydride (Zhuang,

d

VCR 1~

j.I

VLB 11J'Wbl'l1\91..:)\91'W
(Conrard,

uu 1'Y1l '11'\.!f) l1U

d'

1'UU 1Q '1I'H\~~Vllm:;;U~m

1982; Pearce, 1982 U(;1:;;Conrard,

1983)

~1VI un111'l1'il.l

W~CI I'll Cl elfJ

f)(;1fll(;1 eJtll'1~'I11:IJ 11 oifu 1:;; 1t1'l5'11'1'W'Vl1,,:)lfl ir'l5fl11:IJ 'ill flll'l"l":)'I"l1t1~~..:) lJ eJVI 'W'll~ :lJlill ~~ 1:IJlfl

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s iru

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tI 1'W1 \9111'il'W 11(;1:;;'YJ

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q

lJU'W 11.w:IJ~ 'il:;;l~ :lJfll11 'il~ UJl~'U

1\91U~1 cJ..:) l~mm
u
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q

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,

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'lJeJ..:)~ 'WV11eJ1 fll fl' U'I"l":)'I"l1tI ~ of..:)'11,,:)
I'i'W1 oifdj 'WtI 1 offl'I:Jl11 1'1~ 1,,:)"1 1'li'W
hfll'Ul'VI11'W

hflfl11:IJ~'W

1m1\91 hfl'iJ~

hfllJlml~1J

dt
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9J
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Q.I

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91

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cl

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149 'l511~ ~..:)I'W~1'W1'Wii lJf)(;1fll(;1eJtll'1~rllflt1,J

~G)9id

l~ fleJ Vincristine,

'l511~~1":)"1 lW:;; ajamalacine

o'lJ]

QI'::::'

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11J'W\91'W'Wfl1'Vltllfl'1bl'\911 I~'V1lfll1'Vl~,Hl,,:)U(;1:;;

OQ.llf]91~

hflbl'lflt1,J

<j}

lw:;;loifl~'Wtl1'\J'U1:;;~

Vinblastine

~..:)loifl~'Wtl1(;1~fl11:IJ~'W
,

U(;1:;;

cl..J

Q.I

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1m1\91 U~l'cteJ":)'il1flU~lJlill'lJeJ..:)f)(;1fll(;1eJtll'1
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U'I"l":)'I"l1t1~~..:)fl'WeJV1":)U'I"l~ 'VIm tI fll ')

(;1eJtll'1'illflll'l"l":)'I"llt1~~..:)1~
1

l,ril tI~l'VI:IJ 1:;;bl':IJ nl ~'WU 'W1'Vl1":)~ rrun ')tll~:IJ

q

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NPK

lJ

U'W11.w:IJ11 'il:;;Yll1 ,r'l11'V1'I.!flll,r..:) U(;1:;;U~lJlillf)(;1fll(;1 eJtll'1'lJeJ":)U'I"l":)'I"llt1~of

":)l~:IJ~'W

Vinblastine

OH

._./CH3
,0
IN
H:,c

O=C

.'

O-C"
OH

....
CH
3

'OCH3

fl1'n~ 21 flHfft'1~'YI1~lfliJ'tl~~
vinblastine

Vinblastine
~

nmN

at

d'!iI

!iI

1 iu 1nan
"" C1f~
.k
'If 'UfllnflllllJ::::IH'Ul~')j''U~ I~

-'1

1'U1Hn'YI~~~1tH1l'ifflHln'Ue
':.4

lJ)

i!ili

QI

cS..ct.

""

dfj/

lJ)!iI

lJ::::1H~eJlJ'UlmfteJ~'jj''U~
Hodgkin , lJ::::IHtleJ~'jj''U~
non-small cell ,lJ::::IHI~l'UlJ,lJ::::IH1j

_I
-v
lJ"J::::1~fll"Jflt!'ft'U

Vinblastine d'l'UffH~ffti~1~~1Ulfl

1~tI

Robert Noble

une

Charles Thomas Beer mn

1'U'li1~Ulfl~

U'n~'n1t1N4'~
tll::::1t1'jj',r'tl~~
vinblastine ~~lij'Uffl'i~hrNftl'li'Ul~tl1flmJ1lfliJlhu~
,

y.!;t

,.

fi''U'n'U
~~liieJiJfllnhmi'i'Ul'Vi~fillij'U1l1'jj'1
flll'Un flfl'jj'loUri~1,rlfl~flll ft~~1'U
1'Uft~'tl~~lClfml
d

Q,I'

.ci

4'"

Q.I

Cl'

llJ~lft~~'tl11 l'nll::::l1::::'U'U
MlJ'tl~ff'U'Ull!1'U11vinblastine

,d.:

dd~

191

Q.I

4 ....

'U'U'Ul~::::lJlJl::::ff'YItifl1'n
ums

~~~1'UlJ::::IHllJ~m~~'tl111'jj''U
lJ::::IH~~lJ'Ulmft~~
""l

..t

QJ

!it v

fll"Jflmnmr.J1fl'Ufll"J
l'trf.l1

Vinblastine lij'Utlftfllft~ tI~~vm i'UU'n~'n1t1N4'

~ Uft::::lij'U
ms lfliJ~fltl' ltlfli1~ti'U vincristine
~~lij'U~1,j~'tl1H tubulin ~1t11ifllli1'U5~flllnlJ~1ti'U

1~~fft'l~lij'U microtubules 'tlW::::~lij'U

l::::tI::::'tl~~flHUU~lClfftft
1~ml1'nl::::~~U~flHfft'Hmicrotubules iilij'Ulh'Utll::::fl~'U'tl~~
'll

1'YI~f)u[\::::

kinetochore

~~lrhl'il~~tn'hl1'l'Uf)l'J

U~'U11-Wff
'tl~~fll'JUU~lClfft~lJ
iwiff

Ili'Ult1

U'l.i~~1,\HN
lTl'J 1'lJ1C1f'lJ
hl'J::::'YIil~'J::::U::::

10

Vincristine

OH

OC(O)Me

llTW~3 IflHff~"'nn~lIflii'U~H vincristine

..

Vincristine 11J'U~1~flI'li'UI~fJ1
ti'tUl'IJ leurocristine
v

11J'U~10'IJO'lfll1ff11'llff'UlfJilJ
i'l'l~flllft:;l.rt'Ufll';ii'flln

fi~ 11J'U
ij'ftfl1ft ~fJ~~'W'IJ
Iuu

1'I'1'W1
aNi' 'I

hfllJ:;I~'1 hwl'1flflihhufl

...

fll'i~~flqYlli

Tubulin 11J'U
hh~'U ~'1~:;I'I.JgfJ'UlltJft'lI1J'U
microtubules

hw vincristine

"

~:;l!imjfl'l'J\!~'U-vift:;

2 Imftflft IIft:;O'IJO'lfll1ff11'11flHff11'1'U~'1
ilJ 1fl1't!\!ft fll111~flm:;li'l'U~'1 'lu fl1't!\!ft

.
fll1'H aft')f:;~
fl ~fHh:;fJ:;llJ'l'lll.wff'lu msu ti'llCJl'fttlll'IJ'IJ
'lu1

0'

ih hflnfl

"

'rI~ft' 1'W11:;
D:;ii''U ~~dj f-m~~fll1 uti 'I

'U

:,

a'

,t

dq

cv

"

"

tCJl'ftft'l'l~'HlJfl~{Jl~nfltnnlJ'VI~tCJl'ftftlJ~tH
u~rnfllJ~ft~~ ~\Hft1'~ tm~''Um~~fl~1{J
'U

11

;.

.et.

'1161l'1mftltl'YI'l : Allium ascalonicum L.

1..:Jri: AlIiaceae

..

'1166'U9
<!I <!I

."
: "I
u~I9i6fn:J

I'

Ii]'"

cl

..,

mm 11'W1'I6lJiJ1 1'I6lJmfl 1'I6lJ1'I1 Multiplier shallot,

u~I9i~ffl1'l6lJll~'1

Shallot

h fI

1'I611U~..:JliJ'U~'11
tl'1I'U'~'l~ liJ'Umj fUn

'i)lm1V'I1'U'lJ6'1 Prosea
lil'UVlfmn

hfl

No.8 (Vegetables)

H1:'I~ i'li'll1:'l~fmnmHl

..,-

1996 (1'I'U1 65) 'llV'I1'U111'16lJll~'1lJf.!WfflJiJ~

i~ 1~m611111'16lJll~'1lJl9i6mil'U1l1'U"l

f-lfflJtlm.11iT'U

'l

'lu

lJ~'V'l~11111:'l~lfl~6~ lJ M'1$)6~ll-a1111lJ1'V'ltlflUf-l1:'l
unnmmlu l'ItllJll~'1 iJ'I'lf1V1:'I~'l~~iJ111~ 11:'1

~
l~tl~ lm~iJiJiJ'Iltr'Ul~6~t;!~~'U

~1Vf)1'liJn.flflff~

1'I~6tl'l~fltliJtl1l'l1'l

'llV'I1'U'i)lfll'lU'IfftlfflJ'Ui'V'l'lff1'Um~fl'IJ')j'1~

mflQ1fllJ

l'I~tliJn.flfl')j'i!~f-l'l

2539 (m!l

105) 11191U1V1hw1~

1111'16lJll~'1 f-lfflJ'l1lJ tliJll'I ~lltl 'l 1~l'ItllJ~lJ1111~fl lln1'l1~r1~'i) 1Jn lm~ f)'UliI'UVl'lliJ1:'IlJ

urmau 2539

'llV'I1'U'i)lfll'lU'Iff6~fli'V1V-Vlhw

. 'l

'l 1V'I1'U 'i)1fll'lU'Iff6fflJ'U

'V'l'ltl'U~iJ~

~W11:'1'1mWlJ1'I11'V1Vl"V2536 (m!l

(l'I'U1 1) 111'16lJll~'1'1liJ1:'IlJIm~lln1'l1~

0 I 1 m '1f)1 'l~m111';VfflJ'U

205-207) 111111'1tllJll~'1ihff'q'U

i 'V'l'l 1~ VflW 1'i)U U'i)1 n

~"llJ vhiM''iHf)1VtliJ~'U

'IliJ1:'IlJllnYl6'16~lltl'U 'lhVU6Vtl11'1U vhiM'I'i)~ty61l'11'l llniJ1lJt.11 ~l'V'lVl1i 111:'l~lln61f)1'ltlmffiJ

,d

Y.:::::t.

QJ

rI ~.et.

::'t..:!i

9J

..:!i

9J

m'l"lllJ1:'I~1'I6lJll~'1

llflfl'Ul'Utlff~11lJ'U'V'l1l 611'i)V'UI1J'Um6~ 'll'1f)1V,!!iJf-ltllJll'I1:'Itl'l(i')j'llJ1:'I~lll'l'l

5-10 flflJ~lJt.11~lJ)

1'I6lJll~'1ljffUlfltl{c)f~'U

glycosides) 61'i)iltl'ltl'U hfllJ~I~'1 i~

111:'l~ff1n-lm11'U6V~

(quercetin

une

flavonoid

12

\)1fl

m ~1\yHH)'i~ fllJ 1111'H1nYl\)1fl 'hm "It 'i"It1 tl6''U 6'"'ifl1'Hl,j

~luli'a'\JO~

ij

'il C\fn ~ 1.1tn tI ~ lfnH) 1.1"It'lyh

~
, "
Nobel, Beer une Cutts 'uTI 1957 C)f~1i\''YIYl1101.1q'YIllilfl'lhilt1il'UI~Ofl'\JO~111~11tifl
(rat) lI~mr1.1l'f1.1';hiiq'YIf depress bone marrow une peripheral

'U~UIIl'f~l'f1fJNf~

'U'H'Ij'\Jl1

granulocytopenia

\) U tl1 , 'If ~ 1U 1 U I~ fll ft 0 fl '\J11

Vincaleukoblastine

(Vinblastine)

~ 0'

f ;)0

11il ::::l'f 1.111 111 'l ~ 1 ~ 0 0 fl q 'YI

~ "" "
"" , 1.1""
~
C)f~lJog Ul'f'lf U 'l1J1WUOfJlJlfl

Svoboda IrJUlf1'HU ltlW::::ij'li'a l'f1.11111uffnfli\'1fJ

'" ....

n fl il ~

'j/ ""

alcohol '\JO~~UIIl'f~l'f1fJNf ~1111.11'Hl{jfl~1~

IiJ

'\JO~'H'lj1l1.1\)fl'.i(mice) C)f~'YI1'HIflfl ~f1 P-1534 lymphocytic leukemia

""

une

OOfl1J1 2 'lfUfl f10 "Leurosine"

-'l

1iJ2'"

""....

(Vincristine) lIil::::A,,1.1fll~ftfl'lll1\)a

"Vincaleukoblastine"
'j/

6 'lfiifl ~iiq'YIilrJu

L Vincristine (VCR) IrJU drug-of-choice 'Ufll'l1fl'll1

IiJ

'j/

'j/

Aflllil:: AflffflflllfJflffU

ilt01J11'f1.1alkaloid

.
_I........

alkaloids \)1fliltUIIl'f~l'f1afiH

alkaloids 1i\'lJlflfl11 80 ')fiiflll~iil;;fJ~

1flfJ1.I
""

,
"" .
iltOlJ11.1'l'll'YI Lilly

'j/

"leurocristine"

flUOfJ1~ fl11~'\J11~

IiJ

'j/

Afl ff fl flllfJ fl

antitumor
acute leukemia 'UI~fl iifliltnfll~'HlfJ

-'l

1l~ 90%

2,

Vinblastine

''*1fl'll1

Hodgkin's

disease

50-75% lIil::::fJ~',*'U

iifl~nfln'H1fJil~

choriocarcinoma, reticulum cell sarcomas Hil::::monocytic leukemia

3. Leurosine

highly active in tumor system

4. Leurosidine
5. Rovidine

highly active in tumor system

active in P-1534 system

6. Leurosivine active in P-1534 system

ir fll'Y1a1ft1ffiltf1i\'';1fl1~'YIflilO~

lh 1tJ'YIflilO~'U'H\ll'f1.111
w

msnnau

11il::::llfJflfliltl1ilOfJ,\

"

Im::::1i\'~~ojf011 Vinblastine

Vinblastine iiq'YIf';1''lftJ1lJlW'\JO~I~fll~Ofl'\J11ilflUOfJil~
a'

Q.J

tTJ91

il::::llfJflOiltl1ilOfJfl\) 1fll'fnW

~l1J

91

une 1~

~OlJl
~.d

1i\'';1
cv

AlJ'lfUflU Afl1.l~::::lJlW 50 'lfU fl C)f~'U \)1U 1U U \)::::lJOilfl1

1 ~

tI,
4..::11.1
"" ""
,
ilOfJflOg 4 'lfUfl 'YI1J ~::::ff'YI1ifl1l'f Ufl1~1.111.1fl HlflO Vincristine, Vinblastine, Vinrosidine,
.r:k
:t
A;t
~
tI.c::.t
, ,
~
Q.I
Vinleucosine C)f~ffU'YI~4 'lfUflUllJUOilfl1ilOfJfl'YIO~'Ul'f1fl
Dimeric indoleindoline IUO~\)lflOil
A

'"

Q.I

.J""
IiJ 'j/
"'tJ"'"
'j/
,
~
i i
tl1 il 0 fJfl 'YI1J U l'f ~ ~ W A1.1\)::::1.1 ~ 1.11 W U 0 fJ1.11 fl fl U 'If'YIH 1.111.1fl ~ fI ~ fJ~ H
0

~UIIl'f~l'f1m.Jf~'HirfltJ~::::lJlW
ri1U Vincristine ~iifJlJl,*
Iftijfl'\J11 'UI~fllm::::
'Hl0't11IrJUfJlflU

-'l\)~1.1
'" fl il
"

500 fllilfl11J \)::::''lfflilfl1ilOfJ,\ Vincristine 'Hirfll;;fJ~ 1 fl11J l'Jiliru

Vincristine sulphate ',*'hlrJUtnU~I~l'HilO~lftijfl~l

Vinblastine ~iifJlJl,*

Iu hf\lJ::::I~-tI~~

Vinblasine sulphate ',*';1IrJUfJ1Ufll~1'"ilijfllftO~~1

"
',*'l.hu~ hfllJ:a~-:J'U~ijlJlhl'HftO~

13

1 "'"

,
c
~
fll"iIl'lHI9ItHUIUU UJ 'fI9I(;T( mitosis)
G2 OF INTERPHASE

PROPHASE
Early mitotic
spindle

PROMETAPHASE

Aster
/

;J....

Kinetochore
Centromere

+
Nucleolus

Nuclear
envelope

Plasma
membrane

Chromosome, consisting
of two sister chromatids

METAPHASE

Kinetochore
microtubule

ANAPHASE

TELOPHASE AND CYTOKINESIS

Metaphase
plate

Centrosome at
one spindle pole

Spindle

ms uti '119Hlrl'u u u ill 1 'Ylc)fi;Tlil'W ms mhl9HIrl'

lu~UJI~U
u

1fI 'lu ~ 'Iij;1f1'1'Hl

,f

Uft~11ftltll9mftUWl5'W~

1t119Hlrl' 11~fl

'lu ms

Uti'l19Hlrl' l~tJflU

Im III ICJ511( 2n

SI

'lu ms

'lu ~ '1ij;1f119Hlrl'l~

tl1

hi 2n 11~fl n 'lil n )
,

- dJtJff'Wq'~fll'.illti'lICJ5'lrl'u~i~

ilu~'W 1i

1')j''W~')j'

SI

1'W1'W19l"t'Irl''\JtJ':l'i ram

- illijfllnl~~1'W1'W'I1~

~.::!t.::9

.::),

~ ,f fll'.ii;T'.il'li;TIlJ'.ill
'jJ:::'t,f
1'Wi;Tfl1,
une
at

, lJ'lltl'.ilfl

..::::1.::9

, IlfllllUtlll

.::9

.et

.::9

.::),

'\Jfl'l~')j'11'.itJl'WtJWtJ1J~1,

lJ]

!'\Jm::;~fl

""

!'\J'\Jfl'l~')j'
,f ..1

- II 5 '.i::;tI::; nn tJ'WlfltJHn i;T(interphase),

Q

III ICJ511l'vil"l n'W 1l'l~l'vilnulCJ5ftrl'IVl'l

SI

",I

11]

SI

2 1CJ5'lrl'l1111limm

- ~U'Yll'WtJwtJIu'.itylJmtltltJ~

od

l~tJI~ll~

Ilfl'WlI'rJi;T ( anaphase) Im::;m1m'rJi;T ( telophase)

<]

.I

!~'.i 111i;T(prophase),

.....1

Ill'Yllll1 i;T(metaphase),

14

..,

..,

<I

1tl1lfl'J'Uel~&CJJtH'
( cell cycle)

1t)~fll'Uel~l'lH''''
t

Cl

...1

1UJ1ail~ ,s1n:;

'j/

a:; 11~lfll'Htfg

'19J'.c:S

Cl

a tunJ,H'U elW1Hl'"

Cl 'jJ

.d

9J

1\.I'Ull!~~'CJ~"'ii ms

Q;

mH~1 f.Jf~lJ':i~flelll~10 2 ':i~O:; !~Hfl fll':il~':iOll~1 !lll1':ielll 'Vl"~Ull~1fI1U~~fl'j~ll1\.1fll':iUll~

L l:a:;fl\.ll~elfllh,.

( Interphase)

1:;fJdhij'U 1~ fJ~11fI1
fJll~1

~.

flel 1:;1:;GIllJ\.I1:a:;flel'Ufln'ffn~

'JI

i11l~U.u~If.Jf~cfl 'Ul' tl ~ fl'j'Uel~If.Jf~cf U.u~elelmij'U

.k

0'4

""

""

3 1:; fJ~Vel!

.:

'JI

DNA CJ~ICJ~~lJfllll1l'j'tyl~lll~l~lJl1 1:a:;\.I ,,:lJfll1'ff1l.:j

'ffl1llHelVl.:j lfiell~'fffl.:j DNA ''U1:;fJ:;~el it!

- 1:;a: S 1]1'U'j':;fJ:fffH DNA (DNA replication) l~WIf.Jf~"'iiflnl1lityl~ll
ff.:jlflll::-H DNA ~fll

~1111elnfll1~1~el.:jlr11ill1f.Jfll ~fl 11'th~1

~ ~ fl1.l'ri f) 'U!fh fi t!lJ! CJf'U1111Iii u 1( centromere)

.1~U~djfll':i
.,

U~irl1illiCJfllfi~1~el.:j;j'U

'H1ell}rI!'U1~rI f) f ( kinetochore)

fi.:j

.,
1~ U~ U , .g

2. 1::(1:; M (M-phase)
I:;a:

(M-phase)
,

lij\.l1:a:~ijflllu.u~ihlflafJff
11

1 rl1 111lCJfll 1l::nfllmJ~(I'UmJ~~'Hm(l;r'Ulflel'U

1:U:rielfJ ;;3 hUlliff

U~:U.u~'CJfll1l't~l'ff~lJ

~~

ftel'U"'1l:\1flUU.:jUfJfl33fl1l1flfl'U lh:fl3ll~1(1

IlJ1111'flffUel'Ulll'l'ffU~:1'f)l~I'Yl'ff

1UlC\f~"lll~'\fiirl

tfl

t'Jf'UlC\f~"l'if3l63t" ~ t)t'\l3~,"'\f 1C\f~ '\lfl1::~ fl tfi3fff 1~1i1r1lti3r1Url-1

>I

!CJf~cf1Jr:h
'Vill'h !CJf~cf1l:iiflll!l.u.:j~1 3g!fi3lllfl~3~n~1

~.:jm;'1 i~11 !CJf~"'m,;,u 3gl'U1'tl~fl'j

'U3,nCJf~cf~~3r1u~I'lmcflll.:j'\fii~ Irl3U.u~ICJ~ft'lIft1 1l:'1iIl.u-l~18fl~311t!

t!\.I;;3 ICJf~ft'1l::'1iI,;'l

~1'tl~fl'j'Uf)-lICJf~cf8fll,;'1~ GO 1l'Ufl'j::..t.:jICJf~cf'll'11flTW
(cell aging) U~::~l1fJtlt! (cell death)
~'lrlll~ICJf~ft'llWtfii~
1't1~fl'j'Uf).:j!CJf~cf~f)
it!

1l::1ifl~'nf1f)f)~1\.1 GO i'Jl::fJ:n~llld~

Ul1l:fl~ll1JlU,j.:j~l~fl

'lu

01l:t,;'1

15

stage

."

- 1~l1ftl'Ul'U~ff~
o't!
l'fUl'lfftft nflt!

~.nf'U ti'1~fl1:l1flllUli,:jI'lffttlmJ1J'JJ il1~ff 111flflfteJ,:jl1ftl1ninl' 11::

"
~
~
eJ~ 'Ul::V::'UJJlfll1'l~

'lihn

- ifl11JJ l'lfJJ ihlfl1:lw::tll'Unt''U'fJvn'U~

.c::t

QI

- JJfIllff,:jlflll::'H

",

t~fJfl11 nt''U'fJ1fl1JJlii'U ( chromation)

'Q.I.c:S.d

i i ~
"

~~ti'UeJQ ihJJJt'lf'U1l11Iiiv{
1 ml.J

(centromere)
~

'H~eJllfu'UillfleJ{ (kinetochore)

\)dj 2 'U11~VflU~ft::'Ul'U'Ui~Vfl'h lfllJJli1~

~.nr'Utfl'iiJJi'lfJJ

~
(chromatid) l~wlfllJJli1~'t1.JffeJ.J'Ul

"

lfl'ilJJ1'lfJJ'J'ieJU!~tJ'Jti'U l~tJflil sister chromatid ~,:jU'U ti'lifl'iiJJiCJfJJi'UI'lffttl

ifl'iJJlii~

lf~eJIunum ijlf111JJ

"

Isu

'UeJ.J

8 u'J'i~~1l~ii 16

46 u'fi.J ~tJ::ij 92 Ifl1JJlii~

,

- 1::v::i11 fll

2. 1:: V::hhn4ff

IJJI'lfJJl1::ijfl'J1JJVnJJlfll1'l~

( prophase)

e1

Q.I

- l::V::'U IfllJJll1~l1::'H~'fI'J
lfl'i

"'"

DNA 'U'UJJl6fl 11l11'fl'J 'HleJJJfIll111fteJ,:j~fll JJ 'lfJJ6fl 1 'li~ 1I~lt'J.J

'jJ

I~
VfIll'U~I1J'UAflftV'J""'Uft.J l11hfl'H'U

'jJQ.I

l~'lf~! 11'U
JJlfl'U'U11

Iu l'1fJJ 1 u'fi~ii 21fl'iJJlii~

- l~eJ~JJ-u1Ifl~Vff 1I~::-u'Jfl~lml""ff~nvit!
- !'lfu't1~leJft (centrioles)

. . uen

Ifl~eJUi1

1W'lffttlff'VlI1Uft~lWl~ff..1'UN'lfU~

I~U

ffl'H11rJ n

11~

"

',jeJgVllH~llJti'U l'UU~ft::'\i11'lffttl uft~""fvmf'U'tl i,j1~'U (microtubule) l~tlft11 11J

il1~fl ff1JUI~ft ( mitotic spindle) Im::ff1J'UI~ft ivh'l.w{ (spindle fiber) it!lfIl~~I'lf'U il1lliiv{

'UeJ.J

'J}fllfl'iJJliifl ~ru'U leJ'U'1I'1f'Ul1neJft \l.Jii11Jll1~ft ""ilul~ft B'UeJeJflJJllf1fJ'ieJ'UJJlfllJ1VI~Ofll1

IWfftl16{ (Aster) rll'Hf'U1fl'UI'lf~tl~'lf

"

Q.I

Cl'

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