- Comparative Computer Graphics and Solution Studies of the DNA Interaction of Substituted Anthraquinones Based on Doxorubicin and Mitoxantrone
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1-amino>- and 1,4-, 1,5-, and 1,8-bisamino>anthraquinones are shown to intercalate into DNA.Computer graphics modelling of their intercalation into the self-complementary deoxydinucleoside d(CpG) showed differences in binding properties.While the 1-substituted compound can bind from euther groove, the 1,8-disubstituted compound binds with both substituents in the major groove.In the-low energy state of the complex with the 1,5-disubstituted compound, this ligand "straddles" the site with a substituent in each groove-to do this, the compound must bind to a non-base-paired region, so inducing base pairing.The 1,4-compound binds from the major groove; "straddling" is also possible if full minimization of deoxydinucleoside geometry is performed.The differences in binding mode and interaction energies are reflected in the affinities of interaction (1,5- > 1,4- >> 1,8- > 1-); also the antiproliferative effects in vitro are in general agreement with this ranking.
- Islam, Suhail A.,Neidle, Stephen,Gandecha, Bijukumar M.,Partridge, Malcolm,Patterson, Laurence H.,Brown, Jeffrey R.
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- Anti-cancer compounds
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Compounds of formula (I) STR1 in which R1, R2, R3 and R4 are each separately selected from hydrogen, X, NH--A--NHR and NH--A--N(O)R'R" wherein X is hydroxy, halogeno, amino, C1-4 alkoxy or C2-8 alkanoyloxy, A is a C2-4 alkylene group with a chain length between NH and NHR or N(O)R'R" of at least 2 carbon atoms and R, R' and R" are each separately selected from C1-4 alkyl groups and C2-4 hydroxyalkyl and C2-4 dihydroxyalkyl groups in which the carbon atom attached to the nitrogen atom does not carry a hydroxy group and no carbon atom is substituted by two hydroxy groups, or R' and R" together are a C2-6 alkylene group which with the nitrogen atom to which R" and R" are attached forms a heterocyclic group having 3 to 7 atoms in the ring, but with the proviso that at least one of R1 to R4 is a group NH--A--N(O)R'R", and physiologically acceptable salts thereof are of value in the treatment of cancer.
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