Raphael Ben-Shoshan

Synthesis of aminoanthraquinone derivatives and their in vitro evaluation as potential anti-cancer drugs

Abstract Anthraquinones, monosubstituted by aminoalkylamino side chains at positions 1, 2 or disubstituted at positions 1, 5 or 1, 8 were prepared. Their in vitro cytotoxic activity ( ED 50 ) was evaluated using: 1) P388 murine leukemia cells and 2) a subline of these cells resistant to doxorubicin (P388/ADR). The results of the structure—activity relationship analysis indicated that monosubstitution in position 1 or 2 showed a decrease of the activity when compared to adryamicin. Disubstitution in positions 1, 5 by N,N -dimethyl ethylenediamine side chain led to optimal activity, whereas the presence of cyclic dialkylamino substituents in the same positions resulted in a corresponding decrease in the anti-tumor activity. Disubstitution in positions 1,8 did not show any improvement in the cytotoxic activity.

Preparation, characterization and the anticancer activity of a novel series of triaminemonochloroplatinum(II) cations linked to anthraquinone intercalators

Abstract A new series of complexes of the type [PtAm2LCl]+ (where Am = NH3 or Am2 = ethylenediamine and L is a monodentate AQ-Y-(CH2)n-NH2, AQ = anthraquinone, Y = NH, O) was prepared and screened in vitro against P388 leukemia. These complexes displayed higher activities than the corresponding neutral PtAm2L2 1:2 Pt:anthraquinone complexes but lower than the neutral diaminedichloro 1:1 complexes. The [Pt(en)LCl]+ complexes were significantly less active than the cis- and trans-[Pt(NH3)2LCl]+ complexes. The cis and trans isomers displayed similar activities. The complexes bearing the shorter linker chains were more active than those with longer chains. In vivo toxicity studies indicate that they are significantly less toxic than cis-DDP.

Photoreaction of o-quinodimethanetricarbonyliron with pentacarbonyliron

Abstract Irradiation of ( tetrahapio-o -quinodimethane)tricarbonyliron in the presence of Fe(CO) 5 gives three isomeric C 8 H 8 Fe 2 (CO) 6 complexes.

Trapping of Kekulé structures via co-ordination to iron. Positional isomerism in bis-tricarbonyliron complexes of 3,α-dimethylstyrene

meta-Substituted α-methylstyrene and pentacarbonyliron afford on irradiation two isomeric bis-tricarbonyliron complexes, in each of which one of the Kekule structures is trapped.

The effect of cis-platin analogues derived from aminoalkylaminoanthraquinones on DNA cleavage: an electron microscopy study

Abstract The effects of cis -diamminedichloroplatinum(II) ( cis -DDP) and a new analog ( cis -DANAP) derived from aminoalkylaminoanthraquinones (RNH(CH 2 ) 3 NH 2 ) 2 PtCl 2 , R = anthraquinone on the oligonucleotide poly(dG)·poly(dC) were studied by electron microscopy. It was observed that with cis -DANAP, the extent of small fragments increased with the increase of the drug/nucleotide molar ratio (Rb) . This effect was not observed with cis -DDP and with the parent aminoalkylaminoanthraquinone free base. The effect was not time dependent and could be observed only at Rb > 0.4. Explanation for this phenomenon was given on the basis of monoadduct formation between the platinum and purine/pyrimidine bases which leads to strand degradation. A salt effect on the length of poly(dG)·poly(dC) is also present.

Photoreaction of benzocyclobutadienetricarbonyliron with pentacarbonyliron

Irradiation of 1—2a(6a)-η-benzocyclobutadienetricarbonyliron (5) in the presence of Fe(CO)5 gives a mixture of 1—2a(6a)-η : 3-6-η-benzocyclobutadienebistricarbonyliron (6), 1—3a(7a)-η-ferraindenebistricarbonyiiron (3) 1—3a(7a)-η : 4–7-η-ferraindenebistricarbonyliron (4). 1–3a(7a)-η-ferra-2H-indenetricarbonyliron (7), and 1–3a(7a)-η-ferra-2H-indenetricarbonyliron (8); complex (6) is formed via diene-type co-ordination of the four ring π-electrons in (5), while complexes (3), (4) and (7), (8) result from cyclobutadiene ring opening and insertion of an Fe(CO)3 unit.

Ferraindene-iron tricarbonyl complexes by a novel dehydrobromination of o-bromostyrene on photolysis with Fe(CO)5

Irradiation of o-bromostyrene in the presence of Fe(CO)5 leads to the formation of ferraindenetricarbonyliron [C8H6Fe2(CO)6] and ferraindenebistricarbonyliron [C8H6Fe3(CO)9]via dehydrobromination, in addition to complexes derived from direct co-ordination of the original substrate.

Reaction of 1,1-dicyclopropylethylene with pentacarbonyliron: a novel carbon monoxide insertion coupled with a double cyclopropane ring-opening

1,1-Dicyclopropylethylene reacts with pentacarbonyliron to give 2-cyclopropylpenta-1,3-dienetricarbonyliron (V) and, after a longer reaction time, a mixture of (V) and 3-(1′-propenyl)-cyclohex-2-enonetricarbonyliron—a carbon monoxide insertion reaction.