Carl Parson, Valerie Smith, Christopher Krauss, Hirendra N Banerjee, Christopher Reilly, Jeanette A Krause, James M Wachira, Dipak Giri, Angela Winstead, Santosh K Mandal
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 of the metal to DNA bases causes 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. Recently we synthesized a series of novel rhenium pentylcarbonato compounds (PC1-PC6). The rhenium atom in each compound is coordinated to a planar heterocyclic aromatic ligand, thereby forcing each compound to intercalate between the DNA bases. The UV absorption titrations of PC6 with DNA shows hypochromic effect with concomitant bathochromic shift of the charge transfer band at 290 nm. These results suggest that the compound PC6 binds to DNA through intercalation. It is likely that many of the other PC-series of compounds will behave in a similar manner. We have observed that the PC-series of compounds are strong cytotoxic agents against lymphosarcoma (average GI50 ≈ 2.3 ± .6 μM), PC-3 prostate (average GI50 ≈ 2.8 ± 0.6 μM) and myeloid leukemia (average GI50 ≈ 3.0 ± .6 μM) cancer cell lines. The average GI50 values of the PC-series of compounds are much less than the corresponding GI50 values of cisplatin. Also each of the PC-series of compounds exhibits less toxicity than cisplatin in the glomerular mesangial cells.
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