Abstract 4485: Anticancer properties of novel rhenium compounds against human cancer cell lines.

Abstract

Cisplatin, carboplatin, oxaliplatin, and related metallodrugs are extensively being used in the treatment of a variety of cancers. Unfortunately these drugs are highly toxic and tumor becomes drug-resistance. These circumstances have led researchers to look for new cytotoxic agents that may exhibit less toxicity and devoid of drug resistance. It is believed that cisplatin and related drugs directly bind to genomic DNA through purine bases. Synthesis of new metallodrugs which does not follow the above mechanism of action might yield better drugs with less toxicity and devoid of drug resistance. Recently we have demonstrated that several anticancer rhenium compounds do not directly bind to DNA. We have synthesized numerous rhenium pentylcarbonato and acetylsalicylato complexes which include (CO)3(2,2’-Bipyridyl)ReOC(O)OC5H11 (PC-1), (CO)3(1,10-Phenanthroline)ReOC(O)OC5H11 (PC-2), (CO)3(5-Methyl-1,10-Phenanthroline)Re ReOC(O)OC5H11 (PC-3), (CO)3(2,9-Dimethyl-1,10-Phenanthroline)ReOC(O)OC5H11 (PC-4), (CO)3(5,6-Dimethyl-1,10-Phenanthroline)ReOC(O)OC5H11 (PC-5), (CO)3(4,7-Diphenyl-1,10-Phenanthroline)ReOC(O)OC5H11 (PC-6), (CO)3(2,9-Dimethyl-4,7-Diphenyl-1,10-Phenanthroline)Re ReOC(O)OC5H11 (PC-7), (CO)3(2,2’-Bipyridyl)ReOC(O)C6H4·C(O)OCH3 (ASP-1), (CO)3(1,10-Phenanthroline)ReOC(O)C6H4·C(O)OCH3, (ASP-2), (CO)3(5-Methyl-1,10-Phenanthroline)ReOC(O)C6H4·C(O)OCH3 (ASP-3), (CO)3(2,9-Dimethyl-1,10-Phenanthroline)ReOC(O)C6H4·C(O)OCH3 (ASP-4), (CO)3(5,6-Dimethyl-1,10-Phenanthroline)ReOC(O)C6H4·C(O)OCH3 (ASP-5), (CO)3(4,7-Diphenyl-1,10-Phenanthroline)ReOC(O)C6H4·C(O)OCH3 (ASP-6), (CO)3(2,9-Dimethyl-4,7-Diphenyl-1,10-Phenanthroline)ReOC(O)C6H4·C(O)OCH3 (ASP-7). The anticancer properties of the compounds were evaluated using human prostate, alveolar lung, brain, colon, and leukemia cancer cell lines and normal bone marrow cell lines. The results of this study demonstrate that these complexes have significant anticancer properties. Therefore, these complexes can potentially find applications in the treatment of these cancers. Acknowledgment. The work at MSU was partially supported by grants from the National Institutes of Health (Grant No. G11HD038439) and Nuclear Regulatory Commission (Grant No. NRC-HQ-12-G-27-0086). The work at ECSU-UNC was partially supported by grant from the Department of Energy (TMCF/DOE grant). Citation Format: Hirendra N. Banerjee, Deidre Vaughan, Jewe Medley, Gwyn Hyman, Christopher Krauss, Carl Parson, Santosh Mandal, Pola Olczak, Michael Mbagu, Divine Kebulu, Saroj Pramanik, Fazlul Sarkar. Anticancer properties of novel rhenium compounds against human cancer cell lines. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4485. doi:10.1158/1538-7445.AM2013-4485

Synthesis, characterization and cellular location of cytotoxic constitutional organometallic isomers of rhenium delivered on a cyanocobalmin scaffold

“…The IC 50 values for this two species are in agreement with the values reported for similar species both on PC-3 and other cancer cell lines. [13][14][15][16] Compound 2 was the least active of the tested drugs with an IC 50 averaging 15 μM.…”

“…The cytotoxic properties of a number of fac-[Re(CO) 3 (N^N)L] n compounds have been tested on a variety of cancer cell lines with IC 50 values averaging in the low μM range. [13][14][15][16] Furthermore, the emissive properties of the complexes (generally emitting in the yellow/green region of the visible spectrum) has allowed a detailed picture of their cellular distribution. 3,[17][18][19] Reported modifications of the axial or of the diimine ligands of the species, either directed at increasing the inhibitory potency of active compounds or at fine-tuning their emissive properties, tend to increase the hydrophobicity of the complexes.…”