Coenzyme Q10 Analogues: Benefits and Challenges for Therapeutics

Abstract

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.

Aberrant Cerebral Iron Trafficking Co-morbid With Chronic Inflammation: Molecular Mechanisms and Pharmacologic Intervention

“…In addition to these off-the-shelf small molecule anti-oxidants are ones designed based on them, eg, idebenone, a congener of ubiquinone or co-enzyme Q (CoQ) (185)(186)(187). These are quinone-based molecules with redox properties comparable to ascorbic acid and vitamin C. Although CoQ and idebenone have exhibited some therapeutic promise, eg., as in a Phase III clinical trial of the latter in the treatment of Duchenne muscular dystrophy (188), there are no approvals for use although in some European countries it is available in special cases (189).…”

Antioxidant Therapy in Oxidative Stress-Induced Neurodegenerative Diseases: Role of Nanoparticle-Based Drug Delivery Systems in Clinical Translation

“…For e.g., synthetic analogs of CoQ10, idebenone, and mitoquinone (MitoQ) demonstrated effective amelioration of mitochondrial ROS [ 179 ], DNA damage, neuroinflammation, and prevented neuronal degradation [ 180 ]. Idebenone is characterized by a shorter and less lipophilic tail than CoQ10, and MitoQ is composed of ubiquinone and triphenylphosphonium (TPP+) [ 181 ]. Plastoquinone derivatives, i.e., SkQ1 and SkQR1 molecules that contain an antioxidant moiety linked to a lipophilic cation, also demonstrated a neuroprotective effect [ 182 ].…”

Personalized Medicine in Mitochondrial Health and Disease: Molecular Basis of Therapeutic Approaches Based on Nutritional Supplements and Their Analogs

“…Muscle CoQ 10 level is reduced. Primary CoQ deficiencies may respond to exogenous CoQ 10 administration with a general amelioration of the patient clinical conditions [ 39 , 63 , 86 , 116 , 123 , 124 , 125 , 126 , 127 ]. CoQ 10 supplementation is particularly effective in improving symptoms in the myopathies associated with pathogenic variants in ETFDH [ 64 , 65 , 66 ].…”

“…Idebenone, EPI-743, KH176 and more recently all the other cited small molecules have been used in preclinical studies and then employed in clinics for counteracting the mitochondrial respiratory chain defects [ 86 , 123 , 124 , 125 , 126 , 127 ]. EPI-743, already used in clinical trials for the treatment of Leigh syndrome [ 228 ], is now being investigated in clinical trials for its potential usage in the treatment of visual and neurological complications due to a secondary altered redox state in Cbl C deficiency [ 229 ] and in Friedreich ataxia [ 230 ].…”