lettre d`information - Canceropole Grand ouest

!!!"#$!%&'()*+&,*(-!.$+!/)(.0*,+!.$!'&!1$)!$-!2&-23)('(4*$!
!!!5$+/(-+&6'$!.$!'7&#$!8!9)!!9:*'*//$!;(04-(0#!!
!<=>>5=!?7@ABC5D">@CA!
Sommaire
Actualités
2
3
Publications et brevets
!"#$%&'(%)*+,%&'(%!-./.!
!
"2,0&'*,3+!
ECDD"@5=!
0,123451+6! ! ! !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!7/!
8##&!62(943!:+;21(515#;!5;:251%!73(!4%!,3;,%(!!!!!!!!!!!!!!!!!!!!!!!!!!!7-!%1!<!
!!!=+4%,15#;!:%!72'45,315#;6!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!7>!
!
!
 ?%! @3;,+(#7A4%! B(3;:! C2%61! 3! %;$#D+! 6#;! :#665%(! 7#2(! 4%! E(#F(3&&%! @3;,+(#7A4%! -.//)-./>!
GE(#@3;!HHI!J!4KH"@3!4%!-!;#$%&'(%!:%(;5%(L!
!
 ?K+$342315#;!:%6!6%71!@3;,+(#7A4%6!73(!4K0MNM=O!:3;6!4%!,3:(%!:2!E(#@3;!HH!+1351!7(+$2%!4%6!&3(:5!P!%1!
&%(,(%:5!Q!:+,%&'(%!7(#,R35;6L!!
?3!,#;6151215#;!!:K2;!,#&51+!:%!7%(6#;;3451+6!6,5%;15S5T2%6!5;1%(;315#;34%&%;1!(%,#;;2%6! ;K%61!736!
%;,#(%!S5;3456+%!7#2(!:%6!(356#;6!:U5;,#&7315'5451+!:%!,34%;:(5%(L!!
! ! ?KH;615121!"315#;34!:2!,3;,%(!3!:#;,!:+,5:+!:%!(%7#(1%(!,%11%!+$342315#;!J!:%6!:31%6!241+(5%2(%6L!!
?K32:515#;!:2!@3;,+(#7A4%!B(3;:!C2%61!32(3!45%2!4%!V!S+$(5%(!-.//!:%!VR>W!J!/-R/W!:3;6!4%6!4#,32X!
:%!4K0MNM=!J!E3(56L!!
?%6! :31%6! :2! E(#@3;! HH! (%61%;1! 5;,R3;F+%6L! ?%! 7(#F(3&&%! ,#&&%;,%(3! 4%! /%(!Y2544%1!-.//! %1! 6%!
,4A12(%(3!4%!</!:+,%&'(%!-./>L!
F$,,$!'$,,)$!$+,!G!H(,)$!.*+/(+*,*(-!+*!H(0+!+(0:&*,$I!2(110-*J0$)!$-!.$0#!1(,+K!.$0#!'*4-$+!(0!$-!.$0#!
/&4$+!+0)!0-$!1('320'$K!0-!)3+0',&,K!0-$!+(0,$-&-2$!.$!,:L+$K!0-!,$+,!6*('(4*J0$K!0-$!/06'*2&,*(-K!0-$!
.&,$!.$!2(-4)L+!(0!,(0,$!&0,)$!+044$+,*(-M!
;(--$+!BN,$+!.$!O*-!.7&--3$!G!,(0+!P!

-
!!!!
!!!"#$!%&'()*+&,*(-!.$+!/)(.0*,+!.$!'&!1$)!$-!2&-23)('(4*$!
!!!!
QM'&!.3-0,)*,*(-!*-.0*,$!/&)!'$!2&-2$)M!
RCCD!ES5Q!
?3! :+;21(515#;! T25! 3SS%,1%! 2;! F(3;:!
7#2(,%;13F%!:%!7315%;16!4#(6!:2!:53F;#615,!:%!,%(135;6!
,3;,%(6! :5&5;2%! :%! S3Z#;! 5&7#(13;1%! 4%2(! T23451+! :%!
$5%! 73(! 341+(315#;! :%6! ,373,51+6! S#;,15#;;%44%6! %1! :%!
4K321#;#&5%L! =#;! 3773(515#;! ,#;:251! 6#2$%;1! J! 2;%!
6512315#;! :K5&7366%! 1R+(37%215T2%! 5&7#63;1! 2;%!
(+:2,15#;! :%6! 1(351%&%;16! 3;15,3;,+(%2XO! :5&5;23;1!
35;65! 4%6! ,R3;,%6! :%! (+&5665#;L! 066#,53;1! 3;#(%X5%O!
7%(1%! :%! &366%! %1! :%! S#;,15#;! &26,2435(%6! 35;65!
T2K2;%! 5;S43&&315#;! 6D61+&5T2%O! :%6! :+6#(:(%6!
R#(&#;32X! %1! &+13'#45T2%6! G;#13&&%;1! 2;!
RD7%(&+13'#456&%I!(%67#;63'4%6!:K2;!:+6+T2545'(%!:%!
43! '343;,%! +;%(F+15T2%O! 43! :+;21(515#;! ,3;,+(%26%! %61!
2;!6D;:(#&%!,#&74%X%!:#;1!43!7RD65#731R#4#F5%!;U%61!
736!1#134%&%;1!+42,5:+%L!!
M;!-..[O!32!6%5;!:%!4K2;51+!H;6%(&!\V-/!:5(5F+%!73(!4%!
E(! ]#2F;#2XO! 4%! F(#27%O! &%;+! 73(! 4%! E(! @#2%1O!
,#&7#6+! :%! =! =%($356O! ^_! *2&36! %1! @`! ^245%;;%O! 3!
:+'21+! 2;! 7(#Y%1! 62(! 4K+12:%! :%6! &+,3;56&%6!
5&745T2+6!:3;6!4KRD7%(&+13'#456&%!45+!J!43!:+;21(515#;!
5;:251%! 73(! 4%! ,3;,%(L! ?%! F(#27%! 3! 1#21! :K3'#(:!
:+$%4#77+! 2;! &#:a4%! :%! :+;21(515#;! 5;:251%! 73(! 2;%!
,3(,5;#6%! 7+(51#;+34%! ,R%b! 4%! (31! (Dumas' JF' et' al.'
Nutrition'&'Cancer,'2010)L
?%2(! 377(#,R%! &+,3;5615T2%! 6K3772D351! 62(!
4KRD7#1Ra6%! 6%4#;! 43T2%44%!2;%!341+(315#;!:%!43!
7(#:2,15#;! :K+;%(F5%! &51#,R#;:(534%! GF3675443F%!
:K+;%(F5%I!32!;5$%32!R+7315T2%!%1!&26,2435(%!7#2$351!
,#;1(5'2%(!32!:+6+T2545'(%!:%!43!'343;,%!+;%(F+15T2%O!
S3$#(563;1! 43! 7%(1%! :%! 7#5:6! ,R%b! 4%6! 7315%;16!
,3;,+(%2X! :+;21(56L! E#2(! ,#;S5(&%(! ,%11%! RD7#1Ra6%O!
4%! &+13'#456&%! +;%(F+15T2%!&51#,R#;:(534! :2! S#5%! %1!
:2! &26,4%! 6T2%4%115T2%! 3! +1+! +12:5+! 32! 613:%! :%!
:+;21(515#;! 3$3;,+%!,R%b!4%!(31L! ?%6! &51#,R#;:(5%6!
56#4+%6!:%!S#5%!&#;1(%;1!,435(%&%;1!2;%!341+(315#;!:%!
4U%SS5,3,51+!:%!43!6D;1Ra6%!:U0cE!G6,R+&3!/IL!!
!
!
=,R+&3! /!d! _#;,15#;;%&%;1! :%! 43! ,R3e;%! (%675(31#5(%!
&51#,R#;:(534%L!
05;65! 7#2(! S#2(;5(! 43! &f&%! T23;151+! :U0cEO! 4%6!
&51#,R#;:(5%6! R+7315T2%6! :%6! (316! ,3;,+(%2X! :+;21(56!
:#5$%;1! ,#;6#&&%(! -.! g! :U#XDFa;%! G%1! :#;,! :%!
;21(5&%;16I!%;!7426!73(!(377#(1!32X!(316!635;6!G_5F!/3IL!
!
!
B*40)$!T!8!5$-.$1$-,!3-$)43,*J0$!.$+!1*,(2:(-.)*$+!:3/&,*J0$+!'()+!.$!'&!.3-0,)*,*(-!2&-23)$0+$!
&H&-23$!
3I!0cEhC!d!(%4315#;!7(#:2,15#;!:K0cEh,#;6#&&315#;!:KC-!
'I!@#2('%6!:%!"5,R#446!d!,#;6#&&315#;!:KC-!%;!S#;,15#;!:2!7#1%;15%4!:%!&%&'(3;%!
&51#,R#;:(534!
!
@%11%!'3566%!:%!4U%SS5,3,51+!:%!43!6D;1Ra6%!:U0cE!;U%61!736!
:2%!J!2;%!341+(315#;!:%!4U3,15$51+!#2!:2!,#;1%;2!%;!0cE!
6D;1R36%O! &356! J! 2;%! :56657315#;! :%! 4U+;%(F5%!
(%7(+6%;1+%! 73(! 4%! F(3:5%;1! +4%,1(#,R5&5T2%! GijI!
,#;61512+! :%! 73(1! %1! :U321(%! :%! 43! &%&'(3;%! 5;1%(;%!
&51#,R#;:(534%L! M;! %SS%1O! 54! 3! +1+! (%&3(T2+! 2;%!
,#;6#&&315#;! :UC-!3,,(2%!7#2(!&35;1%;5(!2;!&f&%!
F(3:5%;1! +4%,1(#,R5&5T2%!:3;6!4%6!&51#,R#;:(5%6!
R+7315T2%6!:%6!(316!,3;,+(%2X!!:+;21(56!73(!(377#(1!32X!
(316!635;6!G_5F!/'I!(Dumas' JF' et' al.'J' Hepatology,' 2010)L!
\;! 1%4! F3675443F%! +;%(F+15T2%! 32! ;5$%32! :%6!
&51#,R#;:(5%6! R+7315T2%6! 7#2((351! 73(15,57%(! J!!
4URD7%(&+13'#456&%! #'6%($+! :3;6! 43! :+;21(515#;!
,3;,+(%26%L! ?U+4+&%;1! &3Y%2(! 7#2$3;1! %X745T2%(! 4%!
F3675443F%! +;%(F+15T2%! %61! 43! ,#&7#6515#;! 4575:5T2%! :%6!
&%&'(3;%6! &51#,R#;:(534%6! R+7315T2%6L! M;! %SS%1O! 4%!
F(#27%!3!#'6%($+!2;%!S#(1%!32F&%;1315#;!Gj!W.gI!:%!43!
T23;151+! %;! ,3(:5#4575;%6!:3;6!4%6!&%&'(3;%6!:%6!
&51#,R#;:(5%6! R+7315T2%6! :%6! (316! ,3;,+(%2X! :+;21(56!
%;!,#&73(356#;!3$%,!4%6!(316!635;6!G_5F!-3IL!
!
!
?%6!,3(:5#4575;%6!6#;1!:%6!7R#67R#4575:%6!67+,5S5T2%6!:%6!
&%&'(3;%6!&51#,R#;:(534%6!%1!:K5&7#(13;16!(+F2431%2(6!
:%!43!6D;1Ra6%!:K0cEL!?%2(!5&745,315#;!:3;6!4%!F3675443F%!
+;%(F+15T2%! %61! (%;S#(,+%! 73(! 2;%! ,#((+4315#;! 7#6515$%!
%;1(%! 4%2(!T23;151+!%1!43!,#;6#&&315#;!:UC
-!J!4U+131!Hk!
%;!7(+6%;,%!:U#45F#&D,5;%!G_5F!-'I!G:3;6!,%11%!,#;:515#;!!
!
!
!
!
!
!
B*40)$! U!8! 5V'$! /(,$-,*$'! .$+!
2&).*('*/*-$+! +0)! '$! 13,&6('*+1$!
3-$)43,*J0$! 1*,(2:(-.)*&'
hépatique.
a) contenu mitochondrial en
cardiolipine
b) correlation entre quantité de
cardiolipine et consommation d’O2

<
!!!"#$!%&'()*+&,*(-!.$+!/)(.0*,+!.$!'&!1$)!$-!2&-23)('(4*$!
RCCD!ES5Q!
!
43! ,#;6#&&315#;! :UC-!,#&7%;6%!4%!F3675443F%!
+;%(F+15T2%I!L! ?K+T257%!3! ! +F34%&%;1!#'6%($+! :%6!
&#:5S5,315#;6! 65F;5S5,315$%6! :%! 43! ,#&7#6515#;! %;!
3,5:%6! F(36! :%6! ,3(:5#4575;%6L! ?%6! &+,3;56&%6!
7(+,56! (%453;1! 43! T23;151+! %;! ,3(:5#4575;%6!%1h#2!43!
;312(%! :%6! 3,5:%6! F(36! 4%6! ,#&7#63;1! %1! 4%!
F3675443F%!+;%(F+15T2%!:3;6!4%6!&51#,R#;:(5%6!
R+7315T2%6! :%6! (316! ,3;,+(%2X! :+;21(56!6#;1!%;!
,#2(6!:K+12:%L!
!@%! 7R+;#&a;%! :%! F3675443F%!+;%(F+15T2%!6%&'4%!
67+,5S5T2%! 32!S#5%!7256T2%!4%!F(#27%!;K3!736!
(%1(#2$+! 4%6! &f&%6! 341+(315#;6! &51#,R#;:(534%6!
:3;6!4%!&26,4%!6T2%4%115T2%L!
M;S5;O! :K2;! 7#5;1! :%! $2%! ;21(515#;;%4O! ,%6!
,R%(,R%2(6! #;1! 72! &#;1(%(! T2K2;! (+F5&%! %;(5,R5!
%;! R254%! :%! 7#566#;! G/Pg! :%! *i0! %1! Qg! :KME0O!
(%67%,15$%&%;1!3,5:%!:#,#63R%X3+;#lT2%!%1!3,5:%!
%l,#637%;13+;#lT2%I!(%13(:351!4K3773(515#;!:%!43!!
:+;21(515#;!5;:251%!73(!4%!,3;,%(!:3;6!4%2(!&#:a4%!
&2(5;! :%! ,3(,5;#6%! 7+(51#;+34%L! ?%6! &+,3;56&%6!
(%67#;63'4%6! :%! ,%1! %SS%1! (%13(:31%2(! :%6! 3,5:%6!
F(36! 7#4D5;6312(+6!G0BEHI! !;)<! ;%! 6#;1! 736! 45+6! J!
2;%!(+:2,15#;!:%!43!,(#5663;,%!12&#(34%!!%1!(%61%;1!
:#;,!J!%X74#(%(L!!
?%! F(#27%! +12:5%(3! 43! ,5;+15T2%! :K3773(515#;! :%6!
:+6#(:(%6! &+13'#45T2%6! J! :5SS+(%;16!613:%6!:%!43!
:+;21(515#;! 5;:251%! 73(! 4%! ,3;,%(! 3$%,! 2;! (+F5&%!
345&%;135(%!613;:3(:!#2!%;(5,R5!%;!0BEH!;)<!G*i0O!
ME0IL!!
?%6!+12:%6!625$3;1%6!6#;1!+F34%&%;1!%;$563F+%6L!
?%6!7(#7(5+1+6!3;15)5;S43&&31#5(%6! :%6! 0BEH! ;)<!
+13;1!'5%;!:+,(51%6!GWall'et'al.'Nutr.'Rev,'2010I!%1!!
4K5;S43&&315#;! 6D61+&5T2%! +13;1!2;!S3,1%2(!
:+1%(&5;3;1! :%! 43! :+;21(515#;! 5;:251%! 73(! 4%!
,3;,%(O! 4K+12:%! :%! 4K5&73,1! :%6! 0BEH! ;)<! 62(! 4%!
613121! 5;S43&&31#5(%! :2! (31! ,3;,+(%2X! 7%;:3;1! 43!
7(#F(%665#;!:%!43!:+;21(515#;!%61!:#;,!5&7#(13;1%L!
?%! c"_)mO! 4K2;%! :%6! 7(5;,5734%6! ,D1#n5;%6!
5&745T2+%6! :3;6! 4K5;:2,15#;! :%! 43! :+;21(515#;!
,3;,+(%26%! GTisdale,' Physiol.' Rev.,' 2009I! ! Y#2%! 2;!
(A4%! ,%;1(34! :3;6! :5SS+(%;1%6! 731R#4#F5%6!
R+7315T2%6! GReddy' and' Hashimoto,'Annu.'Rev.'
Nutr,'2001;'Reddy'and'Rao,'AM,'J.'Physiol.'
Gastrointest.' Liver'Physiol,'2006IL! ?KRD7#1Ra6%!! :2!
F(#27%! %61! 43! 625$3;1%d! 4%6! 7(#7(5+1+6! 3;15)
5;S43&&31#5(%6! :%6! 0BEH! ;)<! (%13(:%(35%;1!
4K3773(515#;! :2! F3675443F%! +;%(F+15T2%! :3;6! 4%6!
&51#,R#;:(5%6! :%! S#5%! %;! (+:2563;1! 43! 7(#:2,15#;!
:%!,D1#n5;%6!7(#)5;S43&&31#5(%6L!
?K321(%! +12:%! T25! 6%(3! &%;+%! ,#;,%(;%! 4%6! EE0N6!
GE%(#X56#&%!E(#45S%(31#()0,15$31%:!N%,%71#(6IL!!!
?%6!0BEH!;)<!6#;1!4%6!45F3;:6!;312(%46!:%6!EE0N6L!E426!
67+,5S5T2%&%;1O!EE0Nm!%61!2;!(+F2431%2(!,313'#45T2%!
:%!4K+;%(F5%!GChawla'et'al,'Cell,'1994;' Tontonoz' et'al,'
Cell,' 1994;' Wang' et' al,' 2003I! %;! &#:243;1!
4K%X7(%665#;! :%6! Fa;%6! :%6! %;bD&%6! :2!&+13'#456&%!
4575:5T2%! G@Ec)/O! _311D! 3,D4)@#0! #X5:36%LLLI! %1! %;!
615&243;1! 4K#XD:315#;! :%6! 3,5:%6! F(36! G:3;6! 4%6!
&51#,R#;:(5%6O! 7%(#XD6#&%6! %1! &5,(#6#&%6I! 7#2(!
S#2(;5(!:%6!62'61(316!J!:K321(%6!156626L!!
?KRD7#1Ra6%!+&56%!%61!T2%!/I!EE0Nm!%61!5&745T2+!:3;6!
4%!F3675443F%!:%!4K+;%(F5%!&51#,R#;:(534%!:3;6!4%!S#5%!
7#2(! 4%! &#:a4%! :%! ! :+;21(515#;! 5;:251%! 73(! 4%! ,3;,%(!
,R%b!4%!(31!%1!-I!T2%!4%6!%SS%16!'+;+S5T2%6!:%6!0BEH!;)<!
:3;6! ,%! &#:a4%! 3;5&34! 6#;1! :26! J! 4%2(6! 7(#7(5+1+6!
;312(%44%6!:%!45F3;:6L!
!
?3! 7#2(6251%! :%! ,%! 7(#Y%1O! S3563;1! 73(15%! :2!
E(#F(3&&%! @3;,+(#7A4%! -.//)-./>O! ;+,%6651%(3! 2;!
43(F%! 73;%4! :K377(#,R%6! %X7+(5&%;134%6! J! 73(15(!
:K+$342315#;! in' vivo!:2!&+13'#456&%!73(!,34#(5&+1(5%!
5;:5(%,1%! $%(6! 2;%! :+1%(&5;315#;! in' vitro!:%!43!
7R#67R#(D4315#;!#XD:315$%!&51#,R#;:(534%L!
!
906'*2&,*(-+!!
!
) )! *2&36! ^_O! B#27544%! @O! E5;3241! `O! _3;:%2(! ?O!
]#2F;#2X! EO! =%($356! =O! @#2%1! @L! ")<! E\_0)%;(5,R%:!
:5%1! :%43D6! 1R%! #,,2((%;,%! #S! ,3;,%(! ,3,R%X53! 5;! (31!
o51R! 7%(51#;%34! ,3(,5;#656L! G-./.IL! Nutr' CancerL!
[-G<Id<><)W.L!
!
)! *2&36! ^_O! B#27544%! @O! ^245%;;%! @`O! E5;3241! `O!
@R%$345%(!=O!]#2F;#2X!EO!=%($356!=O!@#2%1!@L!MSS5,5%;,D!
#S! #X5:315$%! 7R#67R#(D4315#;! 5;! 45$%(! &51#,R#;:(53! 56!
:%,(%36%:! 5;! 3! (31! &#:%4! #S! 7%(51#;%34! ,3(,5;#656L!
G-./.IL!J'HepatolL!:#5d/.L/./[hYLYR%7L-./.L.QL./-!
!
F(-,&2,+!
!
E,$/:&-$!E$)H&*+!8!!61%7R3;%L6%($356p2;5$)1#2(6LS(!
F:&)'$+!F(0$,!8!,#2%1p&%:L2;5$)1#2(6LS(!
W$&-! B)&-X(*+! ?01&+!8! Y%3;)S(3;,#56L:2&36p2;5$)
1#2(6LS(!
F'(3! D*1+Y! W0'*$--$8! ,4#%&5&6DLY245%;;%p%12L2;5$)
1#2(6LS(!
QM'&!.3-0,)*,*(-!*-.0*,$!/&)!'$!2&-2$)M!

>
!!!!
!!!"#$!%&'()*+&,*(-!.$+!/)(.0*,+!.$!'&!1$)!$-!2&-23)('(4*$!
!!!!
!
!
!
!
!
!
!
E3'$2,*(-!.$!/06'*2&,*(-+!.$+!3J0*/$+!.$!'7&#$!/(0)!'7&--3$!UZTZ!
F(-,&2,8!"0)()$!?(0&0.[<$2&*''$K!2:&)43$!.$!2(().*-&,*(-!
.(0&0.\1$.M0-*H[,(0)+MO)![!ZUM]^M_`M`ZMab!
"!+0*H)$QM!
5$1$)2*$1$-,+!G!W$&-[B)&-X(*+!?01&+K!E,3/:&-$!E$)H&*+!$,!G!F'(3[D*1+Y!W0'*$--$!/(0)!'$0)!
/&),*2*/&,*(-!G!'&!)3.&2,*(-!.$!2$,,$!'$,,)$M!
)!c3'31,R;5n)N%'544#;!0O!02'+!@O!]3nn345!iO!*%432;3D!cO!`3;R!BcO!]4#1!kO!cR#'5%)B3215%(!@O!N%;3241!MO!=#243(:!`O!
E43;,R31! 0O! ?%! q2%61%4! ^rO! ?%! B2+$%4! NO! B2F2%;)B2544#2b#!@O! s32SS&3;;!]O!_%((3;:!rO!i2,!HO!\(F5;!sO!@#;:#;!=O!
?+#;%4!MO!M$35;!`O!?%'(%1#;!^O!^3,T2%&5;!*O!E57%45%(!`O!*2'(%254!*L!M4%,1(#,R%&5,34!6D;1R%656!3;:!,R3(3,1%(56315#;!
#S! 341%(;315;F! 1(57D(5:D4):57D((#4%! &#4%,243(! 61(3;:6! o51R! &241574%! ;51(#F%;)'36%:! :#;#()3,,%71#(! '5;:5;F! 651%6L!
G-./.IL!ChemistryL!/[G<VId//QP[)QVL!
!
)!E#15%(!`O!@R3;1#&%!0O!^#245;!kO!B5(3241!0O!N#F%(!=O!]%66#;!EO!^#2(:3;!`?O!?%F2%;;%,!^rO!]#2F;#2X!EO!k3;:5%(!@L!
cR%!=s<hsG@3I!-L<!7#136652&!,R3;;%4!56!3!;%o!,%44243(!13(F%1!S#(!%:%4S#65;%L!G-./.IL!Br'J'Pharmacol.!!
!
)!*2&36!^_O!B#27544%!@O!^245%;;%!@`O!E5;3241!`O!@R%$345%(!=O!]#2F;#2X!EO!=%($356!=O!@#2%1!@L!MSS5,5%;,D!#S!#X5:315$%!
7R#67R#(D4315#;!5;!45$%(!&51#,R#;:(53!56!:%,(%36%:!5;!3!(31!&#:%4!#S!7%(51#;%34!,3(,5;#656L!G-./.IL!J'HepatolL!
!
)!E#o%(!*EO!?#b3,R!CO!`%5Y%(!?O!B(3D6#;!*iO!@#;;#;!=^L!@#;,56%!6D;1R%656!3;:!@*shB=s!5;R5'51#(D!3,15$51D!#S!1R%!
&5665;F!V)3b373244#;%6L!G-./.IL!Bioorg'Med'Chem'Lett.!-.G/[Id>V>.)>L!!
F(-O3)$-2$+!;*(13.*2&'$+!.$!'cS-*H$)+*,3!.$!>(0)+!
!
/-R!J!/<RO!3&7R51R+t1(%!@O!_3,241+!:%!`+:%,5;%!!
G#(F3;5631%2(!d!=!N#F%(O!H;6%(&!\V-/!u!"21(515#;O!,(#5663;,%!%1!,3;,%(!vI!
!
)!<0-.*!`!.32$16)$!UZTZ8!*(L!C45$5%(! =#(53;5! G\;5$%(651+! :%! "5,%! =#7R53! 0;157#456O! MT257%! 7(#1+5;%6! &%&'(3;35(%6O!
1(3;67#(1O! 65F;3456315#;! %1! 731R#4#F5%6IL!u! `#:24315#;! :%6! ,3;32X! 5#;5T2%6! %X7(5&+6! :3;6! 4%6! ,3;,%(6! 73(! 4%! (+,%71%2(!
65F&3!/!vL!
!
)!%$-.)$.*!TZ!.32$16)$!UZTZ!8!*(L!?32(%;1!=,Ro3(1b!G?3'#(31#5(%!:U5;S#(&315T2%O!M,#4%!E#4D1%,R;5T2%!%1!6%($5,%!:%!
(3:5#1R+(375%! E515+! =347+1(5a(%IL!!u!?%! ,3;,%(! %61! 2;%! &343:5%! &+13'#45T2%d! +$5:%;,%6! %X7+(5&%;134%6! %1! !7%(67%,15$%6!
1R+(37%215T2%6!vL!