In vitro and in vivo Anticancer Effects of a Novel 9-Phenyldibenzo[a,c]phenazin-9-ium Cation and Its Ligands.
BACKGROUND
Multidrug resistance (MDR) is a major problem in cancer treatment. Cu complexes possess the ability to overcome MDR in cancer. Therefore, the search for new Cu complexes is of great clinical significance and we address the anticancer effects of a previously synthesized novel 9-phenyldibenzo[a,c]phenazin-9-ium cation [1(+)] as [1] [CuCl2] and as [1] [I].


METHODS
The existence of the monovalent Cu(I) in [1] [CuCl2] was proven by electron paramagnetic resonance (EPR) studies and in vivo anticancer effects were studied in animals.


RESULTS
The monovalent nature of the Cu ion in [1] [CuCl2] was determined through EPR. The mean survival time of mice bearing doxorubicin-resistant Ehrlich ascites carcinoma cells is longer when [1] [I] is injected intraperitoneally whereas [1] [CuCl2] does not significantly increase the median survival in tumor-bearing mice. Compounds do not follow the immunomodulatory route and only [1] [I] shows cytotoxic activity in both MDR and drug-sensitive leukemia cell lines.


CONCLUSIONS
An organic iodide complex rather than a cupric complex possesses direct cytotoxic potential.
Department of In Vitro Carcinogenesis and Cellular Chemotherapy, Chittaranjan National Cancer Institute, Kolkata, India.
Satyajit
S
Das
Kaushik
K
Banerjee
Manas Kumar
MK
Biswas
Ranjan
R
Bhadra
Prasanta
P
Ghosh
Soumitra Kumar
SK
Choudhuri
D000818:Animals; D000970:Antineoplastic Agents / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use*; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002412:Cations; D045744:Cell Line, Tumor; D003300:Copper / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000502:physiology; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods; D006801:Humans; D008024:Ligands; D008297:Male; D051379:Mice; D010619:Phenazines / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D002412:Cations; D008024:Ligands; D010619:Phenazines; D003300:Copper; C029892:cupric chloride