Targeting glioma with heteroaromatic alkaloids: A review of potential therapeutics

Glioblastoma multiforme (GBM), classified as a grade IV astrocytoma, is the most aggressive and deadly form of glioma, characterized by rapid progression, extensive genetic heterogeneity, and resistance to conventional therapies. Despite advancements in surgical techniques, radiation therapy, and the frontline chemotherapeutic agent temozolomide, the prognosis for GBM patients remains poor, with a median survival of 15 months and a 5-year survival rate of approximately 7 %. The absence of effective long-term treatments underscores the urgent, unmet clinical need for novel therapeutic strategies to improve patient outcomes. Natural products, particularly alkaloids, have garnered attention as a rich source of bioactive compounds with diverse pharmacological properties. Alkaloids, a structurally diverse group of natural products, are renowned for their chemotherapeutic properties and ability to cross the blood-brain barrier (BBB), making them promising candidates for glioma therapy. This review systematically examines all reported heteroaromatic alkaloids with documented anti-glioma activities, highlighting their mechanisms of action where available. By providing a comprehensive resource, it aims to facilitate the identification and optimisation of alkaloid-based compounds for glioma-targeted drug discovery. Additionally, this review emphasizes the importance of incorporating natural products into the drug development pipeline to address the pressing challenges associated with glioma, particularly GBM treatment.