A novel alkenyl-substituted ansa-zirconocene complex with dual application as olefin polymerization catalyst and anticancer drug

Synthesis, Cytotoxicity, and Insight into the Mode of Action of Re(CO)3 Thymidine Complexes

“…No differences in competitive inhibition were observed, however. Although an exact IC 50 value could not be determined for complex 50, our results suggest that the substrate activity of 50 is approximately 10-fold lower than that of AZT. These observations are in accord with results reported by Schibli and co-workers, who recently reported a series of neutral N3-conjugated dThd Re/Tc tricarbonyl complexes and found that the extent of phosphorylation is dependent on the spacer length separating dThd and the organometallic core.…”

“…In a different study, the IC 50 values of 5-fluorouracil and doxorubicin were determined to be 9.19 and 7.88 mm at 96 h, respectively. [48] Other metal-based anticancer agents are organometallic osmium(II) arene complexes with IC 50 values of 24 mm at 24 h and chloro half-sandwich osmium(II) complexes, with the most toxic complex possessing an IC 50 value of 6.4 mm at 24 h. [46,47,49] An alkenyl-substituted ansa-zirconocene complex showed moderate toxicity against A549 cells with an IC 50 value of 136.4 mm at 96 h. [50] An octaazacyclotetracosane dizinc(II) complex has been described as a potent inhibitor of tumor growth, and its IC 50 was determined to be 8.8 mm at 48 h. [51] In contrast, organic chiral salicyl diamines are potent anticancer molecules, with IC 50 values in the range of 0.8-1.8 mm at 48 h. [52] In this study, it was found that out of four different positions, conjugation of the rhenium chelate function to either position C5' of the ribose sugar or position N3 of the pyrimidine base resulted in the most potent organorhenium complexes. A general trend could be established in which an increase in toxicity could be achieved with increasing tether length between the biomolecule and the complex entity.…”

“…The IC 50 value for non-radioactive dThd, used as a control, was determined to be 8.8 AE 3.9 mm for the cell lysate experiment and 48 AE 4 mm with purified recombinant hTK-1. AZT was used as a control in the case of the recombinant enzyme, and its IC 50 value was determined to be 44 AE 15 mm.…”

“…Tc-radiolabeled dThd analogues have received increased attention as noninvasive probes for diagnostic applications, there have been only limited investigations of the antiproliferative properties of rhenium(I) complexes and thus limited reports of IC 50 values for such compounds. [27,28] We recently reported a rhenium(I)-folic acid conjugate that exhibited greater toxicity than cisplatin in a screen against a doxorubicin-and cisplatin-resistant human ovarian cancer cell line (A2780/AD) overexpressing the folate receptor.…”

Metallocenes

“…Titanocene dichloride (7) and some zirconocenes (8) have been reported to be anticancer agents, whereas Cp 2 ZrCl 2 has been identified as a mutagen in at least one toxicological report (9). Prudence dictates caution in handling metallocenes, particularly those with polycyclic aromatic groups.…”