In vitro study on biological efficiency of two tenocyclidine compounds -TCP and TAMORF

Tenocyclidine - TCP presents a broad spectrum of pharmacological activity including antidotal effect in organophosphorus compounds poisoning, radioprotective and anticancer effects. In present study in vitro interactions of TCP and its adamantane derivative - TAMORF with human erythrocyte acethylcholinesterase (AChE) were investigated. The genotoxicity and possible radioprotective activity on human white blood cells were assessed by the alkaline comet assay, viability testing and the analysis of the structural chromosome aberrations. The tested compounds were found to be weak inhibitors of AChE, for TCP IC50 =1x10-5 M and for TAMORF IC50 >1x10-3 M, without reactivating and protective effects on AChE inhibited by soman. Results indicate that TCP modified by the replacement of the cyclohexyl ring with an adamantly ring and piperidine with morpholine group (TAMORF) have lower toxicity. Both compounds have low cytotoxicity and radioprotective activity, but TAMORF also demonstrates cell growth inhibitory effects. To elucidate variations in their biological effectiveness observed in vitro and in vivo, additional analyses are needed. Since TAMORF was found to significantly inhibit cell growth and proliferation in vitro, it seems logically to consider it as a source molecule promising for additional modifications and development of more potent compounds with antitumor properties rather then radioprotector or antidote in organophosphorus poisoning.