Structure–activity relationships and DNA binding properties of apoptosis inducing cytotoxic rhodium(III) polypyridyl complexes containing the cyclic thioether [9]aneS3

Cell‐Selective, Apoptosis‐inducing Rhodium(III) Crown Thiaether Complexes

“…[13] The implicit reversal of ligand-size dependence in comparing the activity of the bpm complex to its phen analogue 6 (IC 50 values: 36.3 AE 6.0 and 72.2 AE 8.0 mm) suggests different mechanisms-of-action may be involved for complexes 8 and 9. This finding prompted us to study and compare the interaction of selected compounds from the series 1-10 with suitable biomolecules.…”

“…These anticancer properties are retained to a varying extent, or even augmented, for specific polypyridyl ligands when k 3 N trispyrazolylmethane (tpm) or k 3 S 1,4,9-trithiacyclononane ( [9]aneS 3 ) are employed as alternative facial coligands in half-sandwich Rh III complexes. [12,13] Considerable in vitro cytotoxicity has also been recently reported for the complex [( [9]aneNS 2 )RhCl 3 ] ( [9]aneNS 2 = 1-aza-4,7-dithiacyclononane) against the ovarian cancer cell line NuTu-19. [14] While the bpy complex [( [9] 2 + is inactive, replacing piperazine with the structurally analogous k 2 S (thiaether) ligand 1,4-dithiane restores cytotoxicity as evidenced by IC 50 values in the range 8.1-11.6 mm.…”

“…20.9 AE 2.8, and 7.4 AE 2.2mM in HT-29 cells. [13] This suggests that different mechanisms-of-action or molecular targets may be involved, depending on pp ligand size within the ([9]aneS 3 )Rh III complexes.…”

“…As DNA fragmentation and mitochondrial permeability measurements using Burkitt-like (BJAB) lymphoma cells have demonstrated that ([9]aneS 3 )Rh III complexes containing the dppz and 2,2'-bipyrimidine (bpm) ligands induce cell-specific apoptosis with only negligible necrosis; [13] such half-sandwich complexes represent a potentially promising class of anticancer agents. We have, therefore, further characterized their structure-activity relationships, with the aim of establishing lead substances, by studying the cell death-inducing properties of novel types of ( [9] 2+ , where pp = bpy, phen, dpq, dppz, bpm, tap (5)(6)(7)(8)(9)(10).…”

“…We have, therefore, further characterized their structure-activity relationships, with the aim of establishing lead substances, by studying the cell death-inducing properties of novel types of ( [9] 2+ , where pp = bpy, phen, dpq, dppz, bpm, tap (5)(6)(7)(8)(9)(10). [13] The most active substances from the series 1-10 were selected for comparative cytotoxicity studies against BJAB lymphoma and leukocyte cells from healthy patients, to establish whether these lead complexes exhibit adequate cell selectivity to justify further investigation.…”