Balzarini, Jan

Hulpia, Fabian

Schols, Dominique

Van Calenbergh, Serge

English

Ghent University Academic Bibliography

TEMP138IN SEARCH OF NOVEL NUCLEOSIDE THERAPEUTICS -EXPLORING THE PURINE CORE OF 3'-C-ETHYNYLADENOSINEFabian Hulpia (1), Jan Balzarini (2), Dominique Schols (2), Serge Van Calenbergh (1)1) Laboratory for Medicinal Chemistry, Ghent University, Ottergemsesteenweg 460, B-9000, Ghent2) Rega Institute for Medical Research, KU Leuven, Minderbroederstraat 10, B-3000, LeuvenNucleoside analogues have been used as therapeutics for the treatment of cancer or viral infections for over 50years. Despite this fact, agents with intriguing and improved efficacy, tolerability etc. have been discovered overthe past decade.1 Hence, we decided to explore untapped potential of certain nucleoside scaffolds.In this work, we set out to elaborate the structure of a potent antitumor agent, 3’-ethynyl-adenosine (EAdo).2 Thepurine ring of EAdo was modified at either the C-2 and / or the C-6 position. Derivatives were screened forcytostatic as well as antiviral activity.Synthetized analogues showed only moderate to no cytostatic activity (IC50>50 µM in proliferation assay),except for EAdo, which confirmed potent cytostatic activity. Furthermore, only one analogue exhibited antiviralactivity against Vaccinia virus, albeit with a modest selectivity index.References1) Jordheim, L. P.; Durantel, D.; Zoulim, F.; Dumontet, C. Nat Rev Drug Discov 2013, 12, 447.2) Hattori, H.; Tanaka, M.; Fukushima, M.; Sasaki, T.; Matsuda, A. J. Med. Chem. 1996, 39, 5005.

In search of novel nucleoside therapeutics: exploring the purine core of 3'-C-ethynyladenosine

https://biblio.ugent.be/publication/6934275/file/6934290.pdf

In search of novel nucleoside therapeutics: exploring the purine core of 3'-C-ethynyladenosine

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Ghent University Academic Bibliography