Antimalaria Drug Development & Pipeline
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چکیده
Artemisin traditionally cleave the peroxide bond by Fe(II) found in heme proteins, thus generating toxic oxygen radicals. Synthetic peroxides, thus are proving to be useful substitutes for artemisinin. The first-generation ozonide OZ277, known as arterolane [1], has been found to inhibit the growth of chloroquine-resistant (K1) and chloroquine sensitive (NF54) parasite strains. In 2012, the combination of arterolane maleate and piperaquine phosphate was released as a 3-day treatment in India [2]. The second-generation peroxide OZ439 (EC50 = 3.4– 4.0nM) is now undergoing Phase IIa studies. It features an 80aryl rather than an 80-alkyl group causing higher stability of the O– O bond towards Fe(II) increasing by 50-fold, presumably because of steric reasons. This in turn translates into a much longer half-life in both rats (t1/2 = 20 h for OZ439 vs. 1h for OZ277) and humans (t1/ 2 = 25–30h for OZ439) [3].
منابع مشابه
A lesson learnt: the rise and fall of Lariam and Halfan.
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