Coenzyme Q10 (CoQ10 or ubiquinone) is a mobile proton and electron carrier of the mitochondrial respiratory chain with antioxidant properties widely used as an antiaging health supplement and to relieve the symptoms of many pathological conditions associated with mitochondrial dysfunction. Even though the hegemony of CoQ10 in the context of antioxidant-based treatments is undeniable, the future primacy of this quinone is hindered by the promising features of its numerous analogues. Despite the unimpeachable performance of CoQ10 therapies, problems associated with their administration and intraorganismal delivery has led clinicians and scientists to search for alternative derivative molecules. Over the past few years, a wide variety of CoQ10 analogues with improved properties have been developed. These analogues conserve the antioxidant features of CoQ10 but present upgraded characteristics such as water solubility or enhanced mitochondrial accumulation. Moreover, recent studies have proven that some of these analogues might even outperform CoQ10 in the treatment of certain specific diseases. The aim of this review is to provide detailed information about these Coenzyme Q10 analogues, as well as their functionality and medical applications.
Overall, the beneficial effects of CoQ10 on human health and disease treatment are well known. However, there is growing interest among the scientific community for CoQ10 analogues and their presumably optimized performance in antioxidant therapies. In this review we have outlined the chemical improvements that successfully enhance CoQ10 bioavailability: shortening of its isoprenoid chain (idebenone and short chain CoQ analogues); addition of specific radicals to promote its mitochondrial accumulation (mitoquinone); modification of natural analogs to boost their antioxidant effect (plastoquinone); modification of the quinone ring (C6 modifications); and introduction of changes on its isoprenoid chain (decylubiquinone) to diversify its biology, its hybridization with other antioxidants and to enhance its potency (EPI-743). Taken together, these synthetic CoQ10 analogues open the door to new and improved therapies for conditions ranging from mitochondrial diseases to cancer. (Antioxidants (Basel). 2021 Feb; 10(2): 236.)