Researchers at The University of Tulsa’s Oxley College of Health and Natural Sciences are advancing efforts to improve brain cancer treatment through the development of new compounds designed to enhance chemotherapy effectiveness while minimising damage to healthy cells. Associate Professors Angus Lamar and Robert Sheaff are leading the research initiative, which recently resulted in the filing of a patent for the newly developed compounds as potential anticancer agents.

Current treatment options for brain cancer typically involve surgery followed by radiation and chemotherapy. However, treatment remains challenging because brain cancer cells are highly heterogeneous and many drugs struggle to cross the Blood-Brain Barrier (BBB), a protective membrane that limits the entry of therapeutic compounds into the brain.

To address this challenge, Lamar and Sheaff collaborated on the development of analog compounds based on memantine, a drug commonly used to treat Alzheimer’s disease that is known to effectively cross the BBB. The research team focused on modifying the memantine structure to create compounds with improved anticancer properties while retaining the ability to penetrate the brain barrier.

Supported by funding from the Oklahoma Centre for the Advancement of Science and Technology, the researchers developed a new organic reaction method that enabled the incorporation of sulfonamide functional groups into targeted locations of organic molecules. Using this approach, Lamar’s research group produced more than 30 new memantine analogs predicted to cross the BBB.

The newly developed compounds were then evaluated by Sheaff’s laboratory for anticancer activity against glioblastoma cell lines, one of the most aggressive forms of brain cancer. According to the researchers, several of the compounds demonstrated cytotoxicity significantly higher than temozolomide, the current frontline chemotherapy used for brain cancer treatment.

The findings, published in the journal Results in Chemistry, also highlighted the compounds’ ability to inhibit metabolic energy production in cancer cells, representing an alternative mechanism for targeting tumors. One of the analogs demonstrated particularly promising results by showing high potency and selectivity against glioblastoma cells while producing no observable harmful effects on healthy noncancerous cells under the same experimental conditions.

Angus Lamar noted that designing compounds capable of crossing the BBB remains one of the biggest obstacles in brain cancer drug development, as multiple molecular characteristics must be carefully balanced. Robert Sheaff added that the team is encouraged by the discovery of a compound that may selectively target cancerous brain cells without affecting healthy tissue, potentially opening the door for safer and more effective therapies in the future.

The researchers believe the study could contribute to the development of next-generation brain cancer therapeutics capable of improving patient outcomes through enhanced drug delivery and selective tumor targeting.