Molecular dynamics exploration of Lupenone: therapeutic implications for glioblastoma multiforme and alzheimer's amyloid beta pathogenesis.

Neuro-oncological and neurodegenerative disorders, represented paradigmatically by glioblastoma and Alzheimer's disease, respectively, persist as formidable challenges in the biomedical realm. The interconnected molecular underpinnings of these conditions necessitate rigorous and novel therapeutic examinations. This comprehensive research was anchored on the premise of unveiling the therapeutic potential and specificity of Lupenone, a potent phytoconstituent, in targeting the molecular pathways underpinning both glioblastoma and Alzheimer's amyloid beta pathology. This was gauged through its interactions with key protein structures, 5H08 and 2ZHV. An integrative approach was adopted, marrying advanced proteomics and modern computer-aided drug design techniques. Molecular docking of Lupenone with 5H08 and 2ZHV was meticulously executed, with subsequent molecular dynamics simulations providing insights into the stability, viability, and intricacies of these interactions. Lupenone demonstrated profound binding affinities, evidenced by robust docking scores of -9.54 kcal/mol for 5H08 and -10.59 kcal/mol for 2ZHV. These interactions underscored Lupenone's eminent therapeutic potential in mitigating glioblastoma and modulating the amyloid beta pathology inherent to Alzheimer's. The introduction of Proteolysis Targeting Chimeras (PROTACs) further magnified the therapeutic prospects, accentuating Lupenone's efficacy. The findings of this study not only underscore the therapeutic acumen of Lupenone in addressing the challenges posed by glioblastoma and Alzheimer's but also lay a strong foundation for its consideration as a leading candidate in future neuro-oncological and neurodegenerative research endeavors. Given the compelling in-silico data, a clarion call is made for its empirical validation in holistic in-vivo settings, potentially pioneering a new therapeutic epoch in both glioblastoma and Alzheimer's interventions.
(© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)