Bivalent Organophosphorus Compounds—Synthesis and Acetylcholinesterase Inhibitory Activity

Abstract

A series of novel symmetric S,S′-2,2′-(ethane-1,2-diylbis(azanediyl)) bis(2-oxoethane-2,1-diyl) O,O,O′,O′-tetraethyl diphosphorodithioate derivatives (12) was designed and synthesized based on the cluster effect and the multiple binding sites of acetylcholinesterase (AChE). The structures of all the newly synthesized title compounds were characterized by ¹ H and ¹³ C NMR as well as elemental analyses. Their inhibitory activities against AChE were tested, and compound 12b exhibited the best activity (6.60-fold higher than ethion). The results suggested that the compound would bind to the catalytic center and the narrow gorge of the AChE simultaneously.

Supplementary materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfer, and Silicon and the Related Elements for the following free supplemental files: Additional table.

GRAPHICAL ABSTRACT

Keywords:

• Cluster effect
• bivalent organophosphorus compound
• acetylcholinesterase inhibitory activity
• dual binding

Acknowledgments

This work was supported by the National Basic Research Program of China (2012BC11410X) and the Major State Basic Research Development Program of China (No.2010CB126106).

Ruliang Xie and Ting Zhang contributed equally to this work and should be considered as co-first authors.