Estimation and correlation of IC50 for the inhibition of human erythrocyte acetylcholinesterase by cis-diamminediaquaplatinum (II).
The present work addresses the estimation and mode of aquiring fifty per cent inhibition of human erythrocyte membrane-bound acetylcholinesterase (AChE, EC 3.1.1.7) by cis-diamminediaqua-platinum II (DDP), which is presently in clinical trials for use as an antineoplastic drug. It has been recently reported that cisplatin itself has the ability to inhibit the AChE activity in vitro [Al-Jafari, et al, 1995; Kamal and Al-Jafari, 1996]. Therefore, this study was focused on the estimation of the IC50 of AChE inhibition by DDP, and its correlation with reaction times. It was found that 0.0-20.0% and 53.8-94.5% AChE inhibition takes place at 3.0 to 60 minutes after 0.025 and 0.40 mM DDP administration, respectively. The IC50 was proportional to the reaction period, and gave values of 0.057 to 0.918 mMat reaction times ranging from 3.0 to 60.0 minutes, respectively. The DDP has 1025 and 67 times higher inhibitory potency than cisplatin for human erythrocyte AChE at 3.0 and 60.0 minutes reaction time respectively. In the light of these findings, particular attention should be paid to DDP in tumor therapy and its inhibitory effect on AChE must be considered during the decision whether to use it as an antineoplastic drug.
Kamal
M A
MA
Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia.
Bakkar
M S
MS
al-Jafari
A A
AA
D000110:Acetylcholinesterase / Q000097:blood*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004910:Erythrocyte Membrane / Q000201:enzymology*; D006801:Humans; D007700:Kinetics; D013997:Time Factors
D002800:Cholinesterase Inhibitors; D000110:Acetylcholinesterase