Guita Etemad-Moghadam

Synthesis of hybrid “metalloporphyrin-ellipticine” molecules

Abstract The synthesis of hybrid “metalloporphyrin-ellipticine” molecules is reported. These molecules are based on 9-methoxyellipticine and [5-(4-hydroxyphenyl)-10,15,20-tris (4-tolyl)]porphyrin linked by a ten-bond chain, −(CH2)4-CO-NH-(CH2)3−, between the hydroxyl group of the porphyrin and the pyridine nitrogen of the pyrido-carbazole. These molecules have been metallated with manganese, iron or zinc salts.

Cytotoxic hybrid molecules ‘metalloporphyrin–ellipticine’ having a high affinity for DNA

Hybrid molecules ‘cationic metalloporphyrin–intercalators’ have been synthesized which have a high affinity for double-stranded DNA and are able to cleave it at low concentrations; compound (2), an efficient bleomycin model based on a cationic metalloporphyrin, is cytotoxic towards murine leukaemia cells L1210 in vitro; iron and zinc analogues of (2) are less active, despite having the same affinity for nucleic acids.

Dramatic enhancement of the photoactivity of zinc porphyrin–ellipticine conjugates by DNA

Both the fluorescence yield and the yield of singlet oxygen generated from the quenching of the triplet state of two water-soluble hybrid molecules ‘zinc porphyrin-ellipticine’, (1) and (2), are low compared to those of simple zinc porphyrin complexes; both these photochemical properties are dramatically enhanced by addition of calf thymus DNA to solutions of (1) or (2), as a result of the conformation change of these hybrid molecules upon interaction with double-stranded nucleic acids.