Synthetic strategies towards ruthenium-porphyrin conjugates for anticancer activity.
The conjugation of porphyrins to metal fragments is a strategy for making new compounds that are expected to combine the phototoxicity and the tumour-localization properties of the porphyrin chromophore with the cytotoxicity of the metal fragment for additive antitumour effect. We report here the preparation of new classes of porphyrin-ruthenium conjugates with potential bio-medical applications. Ruthenium was chosen because several Ru compounds have shown promising anticancer activity. The conjugation with the porphyrin moiety was accomplished either through peripheral pyridyl rings (e.g.meso-4'-tetrapyridylporphyrin, 4'TPyP) or through bpy units (e.g.meso-(p-bpy-phenyl)porphyrins, bpy(n)-PPs, n = 1-4). The number of Ru fragments attached to the porphyrins ranges from 1 to 4 and the total charge of the conjugates from -4 to +8. Different types of peripheral fragments, both Ru(III) and Ru(II), have been used: in some cases they are structurally similar to established anticancer compounds. Examples are [Na](4)[4'TPyP{trans-RuCl(4)(dmso-S)}(4)] (2), that bears four NAMI-type Ru(III) fragments, or [4'TPyP{Ru([9]aneS3)(en)}(4)][CF(3)SO(3)](8) (3) and [bpy(4)-PP{Ru([9]aneS3)(dmso-S)}(4)][CF(3)SO(3)](8) (9) (en = ethane-1,2-diamine, [9]aneS3 = 1,4,7-trithiacyclononane) that have four half-sandwich Ru(II) compounds. The Ru fragments may either contain one or more labile ligands, such as in 2 or in 9, or be coordinatively saturated and substitutionally inert, such as in 3 or in [bpy(4)-PP{Ru([12]aneS4)}(4)][CF(3)SO(3)](8) (11) ([12]aneS4 = 1,4,7,10-tetrathiacyclododecane). Most of the ruthenium-porphyrin conjugates described in this work are soluble--at least moderately--in aqueous solution and are thus suitable for biological investigations, in particular for cytotoxicity and photo-cytotoxicity tests.
Gianferrara
Teresa
T
Department of Pharmaceutical Sciences, University of Trieste, 34127, Trieste, Italy.
Bratsos
Ioannis
I
Iengo
Elisabetta
E
Milani
Barbara
B
Ostrić
Adrian
A
Spagnul
Cinzia
C
Zangrando
Ennio
E
Alessio
Enzo
E
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D011166:Porphyrins / Q000737:chemistry*; D012428:Ruthenium / Q000737:chemistry*
D000970:Antineoplastic Agents; D056831:Coordination Complexes; D011166:Porphyrins; D012428:Ruthenium