DNA-binding and cytotoxic efficacy studies of organorhenium pentylcarbonate compounds

Abstract

Seven organorhenium pentylcarbonate compounds (PC1-PC7) have been synthesized. DNA-binding studies of the PC-series compounds using electronic spectroscopy and gel electrophoresis suggest that the compounds presumably bind to DNA in an intercalative mode. The intrinsic binding constants for PC4, PC6, and PC7 were found to be 1.6 × 10(4), 3.9 × 10(4), and 4.2 × 10(4) M(-1), respectively. The X-ray structure determinations and density functional theory calculations indicate that the polypyridyl ligands in the compounds are nearly planar facilitating DNA binding through an intercalation mechanism. Cytotoxicity studies of 10 µM pentylcarbonate compounds against HTB-12 human astrocytoma brain cancer cells were studied for 48 h. It was observed that each of the pentylcarbonate compounds is active against the cancer cells. However, under analogous conditions, CRL-2005 rat astrocyte normal brain cells are not affected significantly.

The Effects of Synthesized Rhenium Acetylsalicylate Compounds on Human Astrocytoma Cell Lines

“…The UV titrations of PC1 were reported previously [ 17 ]. The UV titrations of RAC9 were carried out in a similar manner.…”

Design of Rhenium Compounds in Targeted Anticancer Therapeutics

“…The selectivity of Re compounds for cancer cell lines is one of the main advantages over other organometallic drugs such as platinum compounds that suffer from strong side effects. For example, pentylcarbonato Re(CO) 3 compounds induced significant cytotoxic effects at the dose of 10 M for an exposure time of 48h in HTB-12 human astrocytoma brain cancer cells but not against CRL-2005 rat astrocyte normal brain cells [78]. Re(CO) 3 acetylsalicylato complexes showed a very selective cytotoxicity on HTB-12 human astrocytoma brain cancer cell lines and glioblastoma multiforme D54 cell lines versus rat normal brain astrocyte cells [77].…”

“…The UV titration of these complexes showed that their absorbance decreased with addition of DNA without any red shift suggesting that these complexes did not follow intercalation mechanism but were more likely to bind to the minor grooves of the DNA double helix [77]. On the other hand, the structurally similar Re(CO 3 ) pentylcarbonato complexes in which each Re atom was tethered to a nearly planar polypyridyl aromatic ligand, were found to bind through an intercalation mechanism as evidenced by X-ray structure determinations and DFT calculations [78].…”

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.…”