استعرض مصدر Electrochemistry of omeprazole, active metabolites and a bound enzyme model. Possible involvement of electron transfer in anti-ulcer action

==مقتطفات==
Benzimidazole sulfoxides, such as omeprazole 1 (Fig. 1) are potent anti-ulcer agents [l-6]. The proposed mode of action involves inhibition of gastric acid secretion into the lumen of the stomach by blockage of (H+/M+) ATPase (proton pump) of the parietal cell, Umeprazole itself is not the actual inhibitor of the I enzyme, but must be transformed into an “active principle” within the cell [1,3,5].

Two of the most likely active substances are the thiophihc cyclic sulfenamide 2 [I-5], and the radical 6 formed by loss of water and rearrangement 161. Both materials are thought to inactivate the ATPase by binding via mercapto groups [5,6], e.g. formation of 3a from 2. We suggest that a prior or subsequent mechanism may entail electron-transfer (ET) processes (redox chemistry) [7] which might alter enzymatic reactions including proton pumping. The proposed active metabolites contain potential ET functionalities (conjugated iminium [8-lI] or odd electron species [12]). We have previously proposed a similar mode of action for the anticancer agents methotrexate and difluoromethylornithine [8] and for Beta-lactam antibiotics [9-ill. '''Conjugated iminium ions may play a role in proton pumping in the vision process via photo-induced intramolecular ET [13,14]'''. Apparently, the need for transformations such as 1 -+ 2 -+ 3a is not essential in vivo. 


مرجع 13: L. Salem, Act. Chem. Res., 12 (1979) 87.

مرجع 14: A.D. Kauten, LA. Drachcv and V.V. Zorina, Biochem. Biophys. Acta, 1018 (1990) 103.