Synthesis and characterization of water-soluble and photolabile 10-arylisoalloxazines: Tools for studying the mechanism of action of flavin-type antimalarials
✍ Scribed by Kirsch, Peer ;Schönleben-Janas, Annette ;Schirmer, R. Heiner
- Publisher
- John Wiley and Sons
- Year
- 1995
- Tongue
- English
- Weight
- 826 KB
- Volume
- 1995
- Category
- Article
- ISSN
- 0947-3440
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✦ Synopsis
Abstract
Isoalloxazine derivatives such as 1a‐d are promising anti‐malarial agents which act as inhibitors of the antioxidant enzyme glutathione reductase and possibly of other proteins. The molecular mechanism of the pharmacological effects has not been studied in detail because compounds 1a‐d are poorly soluble in aqueous solutions of physiological pH. In the present study we introduce two new types of isoalloxazine derivatives with improved solubility properties: The 10‐aryl‐3‐carboxymethylisoalloxazines 2a‐d, and the isomeric 3‐methyl‐10‐(N‐methylpyridiniumyl)isoalloxazine salts 3 and 4. In addition, for the purpose of photoaffinity labeling experiments, the 10‐aryl‐8‐azido‐3‐methylisoalloxazine 5 was designed. The syntheses and characterizations of these new flavins as well as an alternative synthetic approach to the known antimalarials 1a‐d are described.