TY - JOUR
T1 - Water-soluble benzoheterocycle triosmium clusters as potential inhibitors of telomerase enzyme
AU - Colangelo, Donato
AU - Ghiglia, Annalisa
AU - Ghezzi, Annarita
AU - Ravera, Mauro
AU - Rosenberg, Edward
AU - Spada, Fabrizio
AU - Osella, Domenico
N1 - Funding Information:
This work was financially supported by MIUR (Roma) within COFIN2001 project. We are indebted to Johnson Matthey (Reading, UK) for a generous loan of OsO 4 and K 2 PtCl 4 . AR.G. thanks Consorzio CIRCMSB (Bari) for research fellowship. This research was carried out in the frame of the European Cooperation COST D20 action (metal compounds in the treatment of cancer and viral diseases) and COST B16 action (multidrug resistance reversal). Finally, we are indebted to a Referee for the useful and detailed suggestions.
PY - 2005/2
Y1 - 2005/2
N2 - We have studied the ability of several bioorganometallic clusters [(μ-H)Os 3(CO) 9(L)(μ 3-η 2- (Q-H))], where L = [P(C 6H 4SO 3Na) 3] or [P(OCH 2CH 2NMe 3I) 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.
AB - We have studied the ability of several bioorganometallic clusters [(μ-H)Os 3(CO) 9(L)(μ 3-η 2- (Q-H))], where L = [P(C 6H 4SO 3Na) 3] or [P(OCH 2CH 2NMe 3I) 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.
KW - Anti-proliferative agent
KW - Antitumor chemotherapy
KW - Osmium clusters
KW - Quinoline
KW - Telomerase
UR - http://www.scopus.com/inward/record.url?scp=11044225124&partnerID=8YFLogxK
U2 - 10.1016/j.jinorgbio.2004.10.027
DO - 10.1016/j.jinorgbio.2004.10.027
M3 - Article
SN - 0162-0134
VL - 99
SP - 505
EP - 512
JO - Journal of Inorganic Biochemistry
JF - Journal of Inorganic Biochemistry
IS - 2
ER -
