ࡱ>  @!bjbjʚʚ 4$jjjjjjj~&&&&,R ~#j[[[~$'Ry9j[[jj jj~ ~ jj ^ O}2& ^ b0# #b .# ~~jjjj#j [vT %Di[[[~~Dd ~~interakcija derivata DBTAA sa DNA / RNA i antiproliferativni u inci na humanim stani nim linijama Interaction of DBTAA derivatives with DNA / RNA and antiproliferative effects on human cell lines Marijana Radi Stojkovi,a Ivo Piantanida,a Marijeta Kralj,b Marko Marjanovi,b Dariusz Pawlica,c and Julita Eilmesc aLaboratory for Supramolecular and Nucleoside Chemistry, Division of Organic Chemistry and Biochemistry, Ruer Boakovi Institute, PO Box 180, HR-10002 Zagreb, Croatia bLaboratory of Functional Genomics, Division of Molecular Medicine, Ruer Boakovi Institute,PO Box 180, HR-10002 Zagreb, Croatia cDepartment of Chemistry, Jagiellonian University, Ingardena 3, 30-060 Krakw, Poland Previous reports from our laboratory have described the binding properties of a series of dibenzotetraaza[14]annulenes (DBTAA) derivatives (1, 2( (Scheme 1).  EMBED ISISServer  Scheme 1. Previously studied dibenzotetraaza[14]annulenes (DBTAA) derivatives (1, 2(. We now report the binding activity of a new series of DBTAA derivatives studied by electronic absorption, circular dichroism and fluorescence spectroscopy, as well as by thermal melting experiments. The intensive hypochromic and batochromic effect in UV/V&(468DFNz    ʸʸʔʔʔʂppppeZh;hf6mH sH h;hmH sH "h;h5;CJaJmH sH "h;hM5;CJaJmH sH "h;hWK5;CJaJmH sH "h;hdM5;CJaJmH sH "h;h>55;CJaJmH sH "h;h7'5;CJaJmH sH "h;h&X5;CJaJmH sH "h;he7C5;CJaJmH sH ! v x x z ]u  !gdd $7$8$H$a$gdO $7$8$H$a$gd; $7$8$H$a$gd.a? $7$8$H$a$gdM$a$gdf6 $7$8$H$a$gd1a $7$8$H$a$gdd $7$8$H$a$gdf6!   $ & ( * , J L N r t v x z H J v x z ϶詗ufWh;h(GCJaJmH sH h;hf6CJaJmH sH  h;hMCJPJaJmH sH  h;h.a?CJPJaJmH sH #h;h.a?CJH*PJaJmH sH h;hf6CJmH sH h;h1aH*PJmH sH h;hMmH sH h;h.a?H*PJmH sH h;h.a?mH sH h;hf6mH sH h;hMH*mH sH 35:;<GHIMNZ[\]^qrst³€qfRCqjh~i,hOUmH sH 'jEH h~i,h;CJUVmH sH h~i,h;mH sH jh~i,h;UmH sH h~i,hwCJaJmH sH " j]h~i,h;CJaJmH sH " j[h~i,h;CJaJmH sH h~i,h;CJaJmH sH h~i,h(GCJaJmH sH h;h(GCJaJmH sH h;hWKCJaJmH sH  h;hWKCJPJaJmH sH *46HMTUZu~୞sqsbh;hCJaJmH sH Uh;h;CJ\aJmH sH hOCJaJmH sH h;hbCJaJmH sH h;h(GCJaJmH sH h;h;CJaJmH sH " j]h~i,h;CJaJmH sH " j[h~i,h;CJaJmH sH h~i,h;CJaJmH sH  h~i,h;CJPJaJmH sH !is titrations, high affinity, strong thermal stabilisation of both, DNA and RNA, similar ICD spectra upon DNA and RNA addition strongly support the intercalation between polynucleotide base pairs as dominant mode of binding for all studied compounds. Antiproliferative effect of studied compounds on human tumor and normal cell lines was consistent with the strength of observed interactions with DNA/RNA, thus implying that interactions with cellular DNA and/or RNA are the most likely targets within the cell. (1( Pawlica, D., Radi Stojkovi, M., SieroD, L., Piantanida, I., Eilmes, J., Tetrahedron 62 (2006) 9156. (2( Radi Stojkovi, M., Piantanida, I., Kralj, M., Marjanovi, M., }ini, M., Pawlica, D., Eilmes, J., Bioorg. Med. Chem. 15 (2007) 1795. (     !!!!!IJoo`h;h#CJaJmH sH  h;hv6CJPJaJmH sH  h;haCJPJaJmH sH " j]h;hwCJaJmH sH h;hwCJaJmH sH " j[h;hwCJaJmH sH h CJaJmH sH hOCJPJaJmH sH  h;h;CJPJaJmH sH  h;hSCJPJaJmH sH 21h:p~i,. A!"#/ $/ % Dd &',-b  c $A? ?3"`?23 <2@2v)KD`!3 <2@2v)K)Y Hw^w4xڽY lTE73o߼KAh#HBgL- h%X BEAIh*i(U%J4|J[J -vlKeiw&/=={g i!8JA·ڏor\9;n7ćO mǙZ~ce,A*SehK+;~txVt>tI.4›PYP8x#/./^Xc͉"mp^FC|<7Ġ!o4Yx= bDBO"u:Һ\ka).\괥2Faݲ{U>þH8J*W"+2!NSbsQgZGa-g &m:SHȋf7q{֕K-1xN9>P*i4@ɀhEK"8!ӝu38C#p*iA5{Eiw ߹i3Nof­z3ʇWpoߠq{+GR3^{c+S-tBMWR--IoQ#[7Oo$pӖ>F[HJu]J'[r-Nx7n ζy7ցQ-{)nrY3Mg+F*ԏta QSH7rZON&kU\YfwVo4O#zf0'Qu>ad[rͳKeP w:;{ѽw" Aa179Uo`ȆZm_d$27l0b֑-̨@!yV@jQT#[&REZ NYRk+I^I%ŠvF~y 8F\SUu&!@6RsB:Ȍ$u:Һe+'%6f"7 X8,dR:k|tu'C;|u'+i"{oi,@}'-TJ5FioΪݩ׏4^J'MafK~&z.鏅wtdyeeVR]nC~u:Һ;e H.``kX)p3 qV `on >:z]WHG'St'_vrD%D&L12A0= S K4\\4 `5a1@e>D,TsQ+ƘA9@f9πJj@+6@r0m<f6^Rt.Sq#5OxvD?/Z9(RɂdA/iKjKE g uuGgc1HFO~o^cvdTINu# .-~~:}Σ/|jTXcBiѩ _ _T*#֬\s_wyWD.[*vyG"t\0byw`ݞӣ`!߸Il#P=9/G1nj_uIQ|QneʢjzQe-jۓ_TQyјqQ]'\UTX͌-Qh IGVY{E mo  /0"#$%&'()*+,-.13456789:;<=>?Root Entry  F`f}2Data WordDocument 4$ObjectPool O}2`f}2_1218884933FO}2O}2Ole CompObj_ObjInfo  FISIS/Draw Sketch ISISServer ISISServer9qNONEOh+'0 ,Xdp     Ole10Native !Ole10ItemName 1Table2#SummaryInformation( LaXY Arialx 06a! Arial KD41(EjRw%-  '-! NNDEC~%-! cC߻DC%-! acC1DC%-  '*-! wCDC%-  '(*-! T9D8.DC%-  '*-! r9DûDC%-  ' (*-! @C]DC%-  ' *-  ' (*-! Arial yD&/DN%-  ' *-! Arial zDDN %-  '*-! h4zDr EC %-  '*-! yD2DC %-  '(*-! DubDC %-  '*-  '(*-! /DŃDC%-  '(*-! vxD1Z EC%-  '*-! Arial nDdDN%-  '(*-! Arial GDDN%-  ' *-! DQDC%-  ' "*-  '%*-! ~DXhDC%-  '"%(*-! DDC%-  '%'*-! EDC%-  '')(*-! ELݺDC%-  ')+*-! *#J4nW]e=$;|-Ia &!86Ouax};Uh8qr2FnruwUwXHai77-1=LLmGNr-9YRac2v^8 YAFGyzOX oLykx B#k5x_"7[@A #;d7?Ou: We>>39;{U[1D*k`rR-49[|K pO W({~d;xie{.45Y3kFLo"# ;> #>5tO(MlNz0.DTluYMvvBJYv@@'[K>XbV2S7h=]k Os P TZ &j w\AZ^HWtX(GN{4+Az~SlqHS.3=6u@