New N,N-dimethylcarbamate inhibitors of acetylcholinesterase: design synthesis and biological evaluation

A series of N,N-dimethylcarbamates containing a N,N-dibenzylamino moiety was synthesized and tested to evaluate their ability to inhibit Acetylcholinesterase (AChE). The most active compounds 4 and 8, showed 85 and 69% of inhibition at 50 mM, respectively. Furthermore, some basic SAR rules were outlined: an alkyl linker of six methylene units is the best spacer between the carbamoyl and dibenzylamino moieties; electron-withdrawal substituents on aromatics rings of the dibenzylamino group reduce the inhibitory power. Compound 4 produces a slow onset inhibition of AChE and this is not due to the carbamoylation of the enzyme, as demonstrated by the time-dependent inhibition assay of AChE with compound 4 and by MALDI-TOF MS analysis of trypsinized AChE inhibited by compound 4. Instead, compound 4 could act as a slow-binding inhibitor of AChE, probably because of its high conformational freedom due to the linear alkyl chain

Synthesis of LoganVir, a new carbocyclic nucleoside analogue

Starting from a natural cyclopentanoid monoterpene belonging to the class of iridoid glucosides called loganin, we performed the synthesis of a new carbocyclic nucleoside, allowing the preparation of a new lead compound, with a potential HIV antiviral activity as an reverse transcriptase competitive inhibitor that we named LoganVir. The stereocontrol of the coupling reaction was completed utilizing the procedure described by Mitsunobu with a purinic base

Anti-HIV agents from nature: natural compounds from hypericum hircinum and carbocyclic nucleosides from iridoids

The presence of antiviral compounds in the Guttiferae family as medicinal plants and the long traditional use of species of the genus Hypericum for the treatment of many viral infections have developed a strong interest. Among the natural products of plant origin, the ones from Hypericum genus were cited as promising anti-HIV agents. This chapter will report an updated review of carbocyclic nucleoside analogues as anti-HIV agents from iridoids. Moreover, the partial synthesis of antiviral agents from iridoid glucosides to carbocyclic nucleosides as new anti-HIV agents is reviewed