NOVEL PERSPECTIVE ON NEUROPROTECTIVE AGENTS: STRUCTURAL INVESTIGATION OF NEUROMELANIN AND THERAPEUTIC POTENTIAL OF GREEN TEA CATECHINS

Glioblastoma multiforme (GBM) is one of the most aggressive and lethal forms of brain cancer, characterized by rapid cellular proliferation, diffuse infiltration into surrounding brain tissue, and resistance to conventional therapies. Despite advances in surgical techniques, radiotherapy, and chemotherapeutic strategies, the prognosis for patients remains poor, with median survival rarely exceeding 15 months. Within this context, increasing attention has been directed toward the potential use of neuroprotective agents for preventing neuronal damage, attenuating disease progression, and enhancing the efficacy of existing treatments. In this project, neuroprotective compounds were investigated from both chemical and biological perspectives. Neuromelanin, in particular its melanin moiety, considered to be a phenolic polymer, was analysed using quantitative 31P-NMR spectroscopy. The objective was to elucidate the structure of the melanin component, which remains poorly understood due to its complex nature. In parallel, other phenolic polymers—specifically, the three major catechins found in green tea—were evaluated for their biological activity in glioblastoma cells and healthy neural cells. These natural substances were tested both alone and in combination with standard anticancer drugs. Investigations included IC₅₀ determinations, assessment of synergistic interactions between catechins and chemotherapeutics, enzyme expression analysis via real-time PCR, and evaluation of cell death mechanisms including necrosis and apoptosis. The studies underscored the intrinsic challenges in characterizing melanin due to its structural complexity and low solubility under basic conditions. Conversely, catechins demonstrated promising activity in counteracting glioblastoma cell proliferation, suggesting their potential role as adjunctive agents in brain cancer therapy.