Antioxidant and Metal Chelating Strategy by Small Molecule to Overcome the Ischemic Stroke Damage by Inhibiting Fenton Catalytic Reaction in In vivo

Kundu, Joyjit (2025) Antioxidant and Metal Chelating Strategy by Small Molecule to Overcome the Ischemic Stroke Damage by Inhibiting Fenton Catalytic Reaction in In vivo. Masters thesis, Indian Institute of Science Education and Research Kolkata.

Text (MS Dissertation of Joyjit Kundu (20MS072)) 20MS072_Thesis_file.pdf - Submitted Version Restricted to Repository staff only Download (2MB)

Abstract

Ischemic stroke, responsible for nearly 80% of all stroke cases, remains a leading cause of mortality and long-term disability globally. The pathological cascade triggered by cerebral ischemia involves oxygen and glucose deprivation, leading to over production of reactive oxygen species (ROS) such as hydrogen peroxide (H₂O₂). In the presence of redox-active metal ions like Fe²⁺ and Cu⁺, H₂O₂ undergoes Fenton-type reactions, generating highly reactive hydroxyl radicals that cause severe oxidative damage, neuroinflammation, and neuronal death. In this study, we present a novel therapeutic approach combining metal chelation and antioxidant activity through the design of a multifunctional molecule, Ben-O-Gua. This C₃-symmetric guanidinium-based molecule incorporates three key features: (1) primary chelating sites for Cu(I), Cu(II), and Fe(II), (2) a secondary metal-binding domain for enhanced copper coordination, and (3) a benzothiazole moiety that facilitates blood–brain barrier (BBB) penetration. Ben-O-Gua self-assembles into 2D nanosheets in aqueous media, enabling high-density surface presentation of chelating groups and efficient ROS scavenging. The nanosheet exhibits excellent biocompatibility, sustained antioxidative activity, and strong inhibition of Fenton-driven radical generation. Comparative evaluation with structurally modified control molecules confirms the critical role of each functional component in conferring neuroprotective activity. This study introduces a novel nanosheet-based antioxidant platform with dual-functionality, offering a promising strategy for mitigating ischemic stroke-induced neuronal damage.

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