Drug Design for Cerebral Ischemia: A Molecular Perspective Review.

Abstract

Ischemic stroke occurs when reduced or blocked blood flow prevents oxygen and nutrients from reaching brain tissue, resulting in neurological deficits. It is a leading cause of disability and death worldwide, with varying degrees of brain injury, from tissue damage to neuronal death and functional impairments. While restoring blood flow is necessary, it can worsen damage through oxidative stress, pro-inflammatory cytokines, apoptosis, blood-brain barrier disruption, cerebral edema, and hemorrhagic transformation. Neuroprotection plays a crucial role in reducing ischemic damage, with therapies targeting antioxidant, anti-inflammatory, and anti-ferroptotic pathways being essential. Current treatments for ischemia remain insufficient, and there is a lack of comprehensive reviews on drug candidates targeting this condition. This review aims to address this gap by evaluating 271 potential drug candidates for cerebral ischemia. It presents an in-depth analysis of compounds with core structures such as triazole, piperazine, pyrrole, amide, pyridine, and oxadiazole, along with functional groups like hydroxyl, halogen, and alkyl groups. These compounds exhibit promising neuroprotective, antioxidant, anti-ferroptotic, and anti-inflammatory effects. The encouraging findings highlight the need for further research and optimization to develop more effective therapeutic agents, reduce mortality, and prevent permanent disabilities associated with ischemic brain injuries.