title: The effect of novel rhenium compounds on lymphosarcoma, PC-3 prostate and myeloid leukemia cancer cell lines and an investigation on the DNA binding properties of one of these compounds through electronic spectroscopy.
abstract: Despite the tremendous success of cisplatin and other platinum-based anticancer drugs, severe toxicity and resistance to tumors limit their applications. It is believed that the coordination (formation of covalent bond) of the metal (platinum) to the nitrogen bases of DNA cause the ruptures of the cancer as well as normal cells. A search for anticancer drugs with different modes of action resulted in the synthesis of variety of novel compounds. Many of them are in clinical trials now. Recently we synthesized a series of novel rhenium pentylcarbonato compounds (PC1-PC6). The rhenium atom in each compound is coordinated (bonded) to a planar polypyridyl aromatic ligand, thereby forcing each compound to intercalate between the DNA bases. We have investigated the DNA binding properties of one of thePC-series of compounds (PC6) using electronic spectroscopy. The UV absorption titration ofPC6with DNA shows hypochromic effect with concomitant bathochromic shift of the charge transfer band at 290 nm. These results suggest that the compoundPC6binds to DNA through intercalation. It is therefore likely that the otherPC-series of compounds will behave in a similar manner. Thus it is expected that these compounds will exhibit negligible or no side effect. We have observed that thePC-series of compounds are strong cytotoxic agents against lymphosarcoma (average GI50 ≈ 2±2.6 µM), PC-3 prostate (average GI50 ≈ 3±2.8 µM) and myeloid leukemia (average GI50 ≈ 3±2.8 µM) cancer cell lines. The average GI50 values of thePC-series of compounds are 2-3 less than the corresponding GI50 values of cisplatin. Also each of thePC-series of compounds exhibits less toxicity than cisplatin in the glomerular mesangial cells.
authors.affiliation: Department of Biology and Pharmaceutical Sciences, Elizabeth City State University-University of North Carolina, Elizabeth City, NC 27909, USA.
authors.forename: Carl
authors.initials: C
authors.lastname: Parson
authors.affiliation: Department of Biology and Pharmaceutical Sciences, Elizabeth City State University-University of North Carolina, Elizabeth City, NC 27909, USA.
authors.forename: Valerie
authors.initials: V
authors.lastname: Smith
authors.affiliation: Department of Biology and Pharmaceutical Sciences, Elizabeth City State University-University of North Carolina, Elizabeth City, NC 27909, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Krauss
authors.affiliation: Department of Biology and Pharmaceutical Sciences, Elizabeth City State University-University of North Carolina, Elizabeth City, NC 27909, USA.
authors.forename: Hirendra N
authors.initials: HN
authors.lastname: Banerjee
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Reilly
authors.affiliation: Department of Chemistry, University of Cincinnati, Cincinnati, OH 45221, USA.
authors.forename: Jeanette A
authors.initials: JA
authors.lastname: Krause
authors.affiliation: Department of Biology, Morgan State University, Baltimore, MD 21251, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Wachira
authors.affiliation: Department of Chemistry, Morgan State University, Baltimore, MD 21251, USA.
authors.forename: Dipak
authors.initials: D
authors.lastname: Giri
authors.affiliation: Department of Chemistry, Morgan State University, Baltimore, MD 21251, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Winstead
authors.affiliation: Department of Chemistry, Morgan State University, Baltimore, MD 21251, USA.
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Mandal
keywords: DNA binding; PC-3 prostate; Rhenium compounds; bathochromic shift; cancer cells; electronic spectroscopy; hypochromic effect; lymphosarcoma; mesangial cells; myeloid leukemia