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 the PC-series of compounds (PC6) using electronic spectroscopy. The UV absorption titration 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 therefore likely that the other PC-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 the PC-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 the PC-series of compounds are 2–3 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.

Recent Development of Rhenium-Based Materials in the Application of Diagnosis and Tumor Therapy

“…The studies show that they interact with DNA via partial insertion, and the anticancer activity is the same as the DNA-binding activity, which increases with the lipophilicity of the complexes. The Re atoms of the Re complexes Re-16a [ 96 ] and Re-17a [ 97 ] ( Figure 2 ) coordinate with three planar carbonyl and planar polypyridine aromatic ligands to form an octahedral structure. Because of the planarity of aromatic phenanthroline rings, the complexes are forced to insert into the DNA bases.…”

Theoretical Insight into the Medicinal World of Organometallics: Macro versus Nano

“…The other alternative complexes have at least one direct, covalent metal-carbon bond, having structural variety, diverse stereochemistry, provide control over major kinetic properties, kinetically stable, usually uncharged, and having low oxidation state of metal atom, so they can be used as ideal candidates for anticancer candidates [1][2][3][4]. Some examples are: metallocenes [5][6][7][8][9], organometallic ruthenium half-sandwich complexes [10][11][12][13][14], organometallic osmium half-sandwich complexes [15][16][17], organometallic iridium and rhodium complexes [18][19][20][21], rhenium organometallics [22][23][24], ruthenium, osmium, iridium, and platinum organometallics as scaffolds for protein kinase inhibitors, metal NHC complexes [25,26], and metal carbonyl complexes [27,28].…”

“…The remedy is now to search for new compounds with new mode of action to overcome the resistant strains. This can be done by either the organic derivatization of old drugs or completely new organometallic drugs, for example, new tamoxifen [19][20][21]29], platensimycin [22][23][24], etc.…”

“…Studies were carried out on complexes with iron, cobalt or gold, titanium, ruthenium, or gallium central atoms, which have shown the promising results in preclinical studies. Other metal complexes which have shown potential anticancer activity are the complexes of Rh (I), Rh (III) [22,23,47], Ir (I), Ir (II), Ir (IV) [48,20,21], Os (II), and Os(III) [18,[49][50][51][52]. Ferrocifenes [53] exhibit anticancer activity against hormone dependent and hormone-independent breast cancers.…”

Synthesis and Characterization of Novel [2 + 1] Tricarbonyl Rhenium Complexes with the Hydrophilic Phosphine Ligands PTA and CAP

“…In addition to the exploration of the [2 + 1] strategy for the design of new Re(I) complexes by using the appropriate ligands, there is an increased interest on the study of intermolecular interactions of Re(I) complexes in the solid state [ 33 – 35 ] based on diverse types of interactions of rhenium complexes with DNA [ 36 , 37 ]. Similar systematic crystal structure studies [ 38 – 40 ] have revealed the importance of lone pair π and more specifically the role of carbonyl-carbonyl interactions on the supramolecular assembly of Re complexes.…”