Translational Pharmaceutical Perspectives on Quinones as Antioxidant and Antidiabetic Agents in Diabetes and Its Complications.

Abstract

Background: Diabetes mellitus (DM) is an extremely complex metabolic disorder, with many factors contributing to persistent hyperglycaemia, redox dysregulation, and micro- and macrovascular damage over time. There is growing evidence that oxidative stress is one of the main mechanisms of β-cell damage, insulin resistance, and consequent tissue damage, pointing to the need for therapies to modulate metabolic and redox responses. The extensive nature of quinones has revealed that they can be potential dual-acting redox-active compounds that may have antioxidant and antidiabetic activities. Objectives: This review aims to evaluate quinones from a pharmaceutical perspective, considering the chemical diversity and structure-activity relationships, the physicochemical parameters pertinent to drug development, and the mechanisms of action in terms of glucose homeostasis, insulin signalling, mitochondrial protection, and glycoxidative damage. Methods: Narrative review of the evidence from medicinal chemistry, experimental pharmacology, pharmacokinetics, formulation research, and clinical studies of the potential role of quinones in diabetes and its complications. The paper addresses the relationship between chemical structure and biological activity, redox-dependent mechanisms of action, tissue-protective actions, challenges associated with delivery, toxicity, and recent approaches to formulation. Results: Quinones influence several processes implicated in diabetes, including mitochondrial dysfunction, oxidative stress, pancreatic β-cell injury, insulin signalling impairment, AGE-RAGE activation, and chronic inflammation. Currently, CoQ10 has the strongest evidence in humans, while thymoquinone (TQ), pyrroloquinoline quinone (PQQ), anthraquinones, and mitochondria-targeted derivatives have mainly cellular and animal studies to support them. Low solubility, variable systemic exposure, rapid metabolism, and the potential for pro-oxidant effects at high concentrations continue to hamper therapeutic development of these compounds. Conclusions: Future research scopes will rely on rational derivatisation, precision delivery technologies, and clinically validated safety frameworks to translate redox pharmacology into effective therapeutic interventions.