Novel organometallic cationic ruthenium(II) pentamethylcyclopentadienyl benzenesulfonamide complexes targeted to inhibit carbonic anhydrase.
Cationic ruthenium(II) pentamethylcyclopentadienyl benzenesulfonamide sandwich complexes have been synthesized and screened for enzymatic inhibition of the physiologically dominant carbonic anhydrase (CA) isozymes: human CA I and II, mitochondrial isozymes VA and VB, and the cancer-associated isozyme IX. The complexes demonstrated weaker binding to CAs compared with typical aromatic sulfonamides, inhibiting the enzyme at high nanomolar concentrations. An in vitro cytotoxic evaluation of the complexes was also undertaken against a range of tumorigenic cell lines and a healthy human cell line. Complexes inhibited the growth of cancerous cells at low micromolar concentrations while expressing lower levels of toxicity towards the normal human cell line. Factors influencing the synthesis, cytotoxicity, and enzyme affinity for this series of organometallic complexes are discussed.
Loughrey
Bradley T
BT
Eskitis Institute, Griffith University, Brisbane, Australia.
Williams
Michael L
ML
Healy
Peter C
PC
Innocenti
Alessio
A
Vullo
Daniela
D
Supuran
Claudiu T
CT
Parsons
Peter G
PG
Poulsen
Sally-Ann
SA
D000818:Animals; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D012428:Ruthenium / Q000737:chemistry*; D013449:Sulfonamides / Q000737:chemistry*
D002257:Carbonic Anhydrase Inhibitors; D009942:Organometallic Compounds; D013449:Sulfonamides; D012428:Ruthenium; D002256:Carbonic Anhydrases