title: Water-soluble benzoheterocycle triosmium clusters as potential inhibitors of telomerase enzyme.
abstract: We have studied the ability of several bioorganometallic clusters [(mu-H)Os(3)(CO)(9)(L)(mu(3)-eta(2)-(Q-H))], where L = [P(C(6)H(4)SO(3)Na)(3)] or [P(OCH(2)CH(2)NMe(3)I)(3)], and Q = quinoline, 3-aminoquinoline, quinoxaline or phenanthridine, of inhibiting telomerase, a crucial enzyme for cancer progression. In general, quinolines have shown interesting biological properties, especially in inhibiting enzymes. For example, the 2,3,7-trichloro-5-nitroquinoxaline (TNQX) exhibited strong anti-telomerase activity in vitro. Among the quinoline-clusters under study, only the negatively charged ones (by virtue of the sulfonated phosphines) exhibited good anti-telomerasic activity on semi-purified enzyme in a cell-free assay, while they were ineffective in vitro on Taq, a different DNA-polymerase. On the contrary, the treatment of breast cancer MCF-7 cell line did not evidence any activity of these clusters, suggesting a low aptitude for crossing cell membrane. Furthermore, all clusters exhibited non-specific, acute cytotoxicy, probably due to accumulation on cell membranes by virtue of their amphiphilic character. A detailed study of Os uptake and accumulation in MCF-7 cells supported this hypothesis.
authors.affiliation: Dipartimento di Scienze Mediche, Università del Piemonte Orientale Amedeo Avogadro, Via Solaroli 17, 28100 Novara, Italy.
authors.forename: Donato
authors.initials: D
authors.lastname: Colangelo
authors.forename: AnnaLisa
authors.initials: A
authors.lastname: Ghiglia
authors.forename: AnnaRita
authors.initials: A
authors.lastname: Ghezzi
authors.forename: Mauro
authors.initials: M
authors.lastname: Ravera
authors.forename: Edward
authors.initials: E
authors.lastname: Rosenberg
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Spada
authors.forename: Domenico
authors.initials: D
authors.lastname: Osella
mesh_terms: D001693:Biological Transport, Active; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002474:Cell-Free System; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D009992:Osmium / Q000737:chemistry; D019098:Telomerase / Q000037:antagonists & inhibitors*
chemical_list: D004791:Enzyme Inhibitors; D009942:Organometallic Compounds; D009992:Osmium; D019098:Telomerase