Bioactive Pseudo‐C‐nucleosides Containing Thiazole, Thiazolidinone, and Tetrazole Rings

Abstract

The synthesis of new pseudo‐C‐nucleosides was accomplished starting from 3‐O‐benzyl‐1,2‐O‐isopropylidene‐α‐D‐ribo‐pentodialdo‐1,4‐furanose, aiming to build thiazole, triazole, tetrazole, and thiazolidinone derivatives. The stereochemistry of the thiazolidinone epimers was confirmed by DFT/B3LYP calculations. The well‐known diversity of biological activities exhibited by compounds with these heterocyclic moieties in their structure encouraged the investigation of the insecticidal activity against Musca domestica. The thiazole derivative was efficient as insecticide with LD50=6.7 ng/g, which is in the order of the LD₅₀ values for pyrethroids on the same insect. All the compounds tested showed knockdown, mediated through action on the insect nervous system. The neuroactivity found in insects has motivated the evaluation of the inhibition of acetylcholinesterase and butyrylcholinesterase. The two thiazolidinone derivatives tested inhibited butyrylcholinesterase from human serum (36% and 22%), while inhibition of amphiphilic acetylcholinesterase from human erythrocytes at the same concentrations was found to be very low (5% and 8%). This selective activity may indicate potential application of these structures for amelioration of Alzheimer's disease.

Dedicated to the memory of Prof. Jacques van Boom.

Keywords:

• Pseudo‐C‐nucleosides
• Synthesis
• DFT calculations
• Insecticidal activity
• Neuroactivity
• Alzheimer disease

Acknowledgment

The authors thank The British Council and the Ministério da Ciência e do Ensino Superior for financial support and Fundação para a Ciência e Tecnologia for a postdoctoral grant.

Notes

Dedicated to the memory of Prof. Jacques van Boom.