title: Sawhorse-type diruthenium tetracarbonyl complexes containing porphyrin-derived ligands as highly selective photosensitizers for female reproductive cancer cells.
abstract: Diruthenium tetracarbonyl complexes of the type [Ru2(CO)4(l2-g2-O2CR)2L2] containing a Ru-Ru backbone with four equatorial carbonyl ligands, two carboxylato bridges, and two axial two-electron ligands in a sawhorse-like geometry have been synthesized with porphyrin-derived substituents in the axial ligands [1: R is CH3, L is 5-(4-pyridyl)-10,15,20-triphenyl-21,23H-porphyrin], in the bridging carboxylato ligands [2: RCO2H is 5-(4-carboxyphenyl)-10,15,20-triphenyl-21,23H-porphyrin, L is PPh3; 3: RCO2H is 5-(4-carboxyphenyl)-10,15,20-triphenyl-21,23H-porphyrin, L is 1,3,5-triaza-7-phosphatricyclo [3.3.1.1]decane], or in both positions [4: RCO2H is 5-(4-carboxyphenyl)-10,15,20-triphenyl-21,23H-porphyrin, L is 5-(4-pyridyl)-10,15,20-triphenyl-21,23H-porphyrin]. Compounds 1-3 were assessed on different types of human cancer cells and normal cells. Their uptake by cells was quantified by fluorescence and checked by fluorescence microscopy. These compounds were taken up by human HeLa cervix and A2780 and Ovcar ovarian carcinoma cells but not by normal cells and other cancer cell lines (A549 pulmonary, Me300 melanoma, PC3 and LnCap prostate, KB head and neck, MDAMB231 and MCF7 breast, or HT29 colon cancer cells). The compounds demonstrated no cytotoxicity in the absence of laser irradiation but exhibited good phototoxicities in HeLa and A2780 cells when exposed to laser light at 652 nm, displaying an LD50 between 1.5 and 6.5 J/cm2 in these two cell lines and more than 15 J/cm2 for the others. Thus, these types of porphyric compound present specificity for cancer cell lines of the female reproductive system and not for normal cells; thus being promising new organometallic photosensitizers.
authors.affiliation: Institut Universitaire de Pathologie, CHUV, Lausanne, Switzerland.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Schmitt
authors.forename: Mathieu
authors.initials: M
authors.lastname: Auzias
authors.forename: Petr
authors.initials: P
authors.lastname: Stepnicka
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Sei
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Georg
authors.initials: G
authors.lastname: Süss-Fink
authors.forename: Bruno
authors.initials: B
authors.lastname: Therrien
authors.forename: Lucienne
authors.initials: L
authors.lastname: Juillerat-Jeanneret
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002277:Carcinoma / Q000188:drug therapy; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004563:Electrochemistry; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000188:drug therapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011166:Porphyrins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013057:Spectrum Analysis; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy
chemical_list: D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D011166:Porphyrins