A paper co-authored by Vasco Cachatra, Alice Martins, Maria Conceição Oliveira, and Amélia Pilar Rauter has been selected for the cover of Organic & Biomolecular Chemistry.
The article, titled “Purine nucleosides as selective inhibitors of butyrylcholinesterase – a multidisciplinary study“, used a computational study to identify key structural features, namely, the benzyl group at position 2 and the purine acetamido group, as essential for BuChE inhibition. A radiolabelled analogue showed low brain uptake, prompting the synthesis of new analogues. Deoxygenation at various positions led to modest inhibitors, but two compounds with deoxygenation at position 6 and a lyxopyranosyl group showed improved activity (IC₅₀: 3.7–7.8 μM). One was non-cytotoxic at the active dose. Both shared αDN7 stereochemistry, confirming its structural relevance. Synthetic optimization enhanced N7 regioselectivity and increased nucleoside yields from 36% to 52%.