Border between natural product and drug: Comparison of the related benzoquinones idebenone and coenzyme Q10

Coenzyme Q(10) is a ubiquitous component of cellular membranes and belongs to the class of benzoquinones that mainly differ with regards to the length and composition of their hydrophobic tail. The characteristic quinone group can accept electrons from various biological sources and is converted by a one electron transfer to the unstable semiquinone or by a two electron transfer to the more stable hydroquinone. This feature makes CoQ(10) the bona fide cellular electron transfer molecule within the mitochondrial respiratory chain and also makes it a potent cellular antioxidant. These activities serve as justification for its popular use as food supplement. Another quinone with similarities to the naturally occurring CoQ(10) is idebenone, which shares its quinone moiety with CoQ(10), but at the same time differs from CoQ(10) by the presence of a much shorter, less lipophilic tail. However, despite its similarity to CoQ(10), idebenone cannot be isolated from any natural sources but instead was synthesized and selected as a pharmacologically active compound in the 19805 by Takeda Pharmaceuticals purely based on its pharmacological properties. Several recent clinical trials demonstrated some therapeutic efficacy of idebenone in different indications and as a consequence, many practitioners question if the freely available CoQ(10) could not be used instead. Here, we describe the molecular and pharmacological features of both molecules that arise from their structural differences to answer the question if idebenone is merely a CoQ(10) analogue as frequently perpetuated in the literature or a pharmaceutical drug with entirely different features. (C) 2015 The Authors. Published by Elsevier B.V.