Electrochemical Synthesis of the In Human S-oxide Metabolites of Phenothiazine-Containing Antipsychotic Medications
Asra R. Malmakova A.E. Jones A.M.
July 2024Multidisciplinary Digital Publishing Institute (MDPI)
Molecules
2024#29Issue 13
The tractable preparation of Phase I drug metabolites is a critical step to understand the first-pass behaviour of novel chemical entities (NCEs) in drug discovery. In this study, we have developed a structure–electroactivity relationship (SeAR)-informed electrochemical reaction of the parent 2-chlorophenothiazine and the antipsychotic medication, chlorpromazine. With the ability to dial-in under current controlled conditions, the formation of S-oxide and novel S,S-dioxide metabolites has been achieved for the first time on a multi-milligram scale using a direct batch electrode platform. A potential rationale for the electrochemical formation of these metabolites in situ is proposed using molecular docking to a cytochrome P450 enzyme.
chlorpromazine , electrochemistry , metabolite , phenothiazine
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School of Pharmacy, Institute of Clinical Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, B15 2TT, United Kingdom
Bekturov Institute of Chemical Sciences, Almaty, 050010, Kazakhstan
School of Pharmacy
Bekturov Institute of Chemical Sciences
10 лет помогаем публиковать статьи Международный издатель
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