Browsing by Author "Davies, Jill"
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- Diels–alder/thiol–olefin co-oxygenation approach to antimalarials incorporating the 2,3-dioxabicyclo[3.3.1]nonane pharmacophorePublication . O'Neill, Paul M.; Verissimo, Edite; Ward, Stephen A.; Davies, Jill; Korshin, Edward E.; Araujo, Nuna C. P.; Pugh, Matthew D.; Cristiano, Maria Lurdes Santos; Stocks, Paul A.; Bachi, Mario D.Abstract—A Diels–Alder/thiol–olefin co-oxygenation approach to the synthesis of novel bicyclic endoperoxides 17a–22b is reported. Some of these endoperoxides (e.g., 17b, 19b, 22a and 22b) have potent nanomolar in vitro antimalarial activity equivalent to that of the synthetic antimalarial agent arteflene. Iron(II)-mediated degradation of sulfone-endoperoxide 19b and spin-trapping with TEMPO provide a spin-trapped adduct 25 indicative of the formation of a secondary carbon centered radical species 24. Reactive C-radical intermediates of this type may be involved in the expression of the antimalarial effect of these bicyclic endoperoxides.
- Semi-synthetic and synthetic 1,2,4-trioxaquines and 1,2,4-trioxolaquines: synthesis, preliminary SAR and comparison with acridine endoperoxide conjugatesPublication . Araujo, Nuna C. P.; Barton, Victoria; Jones, Michael; Stocks, Paul A.; Ward, Stephen A.; Davies, Jill; Bray, Patrick G.; Shone, Alison E.; Cristiano, Maria Lurdes Santos; O'Neill, Paul M.A novel series of semi-synthetic trioxaquines and synthetic trioxolaquines were prepared, in moderate to good yields. Antimalarial activity was evaluated against both the chloroquine-sensitive 3D7 and resistant K1 strain of Plasmodium falciparum and both series of compounds were shown to be active in the low nanomolar range. For comparison the corresponding 9-amino acridine analogues were also prepared and shown to have low nanomolar activity like their quinoline counterparts.