2020-2021 Faculty Research Grants
Denise Smith and Desmond Murray (Biology, Chemistry)
Hybrid Temozolomides (TMZ) as Potential Antiglioblastoma Agents
The objective of this chemistry – biology collaborative research project is to investigate the synthesis and biological activity of hybrid temozolomides as potential antiglioblastoma agents. Temozolomide (TMZ) is an FDA approved oral chemotherapeutic small molecule (molecular formula: C6H6N6O2; molar mass: 194.151g/mole) prodrug used as a first-line treatment for glioblastoma multiforme (GBM). It is an alkylating agent that works by stopping cancer cells from making DNA. TMZ readily penetrates the blood-brain barrier and methylates the N-7 or O-6 positions of DNA guanine residues which damages the DNA and triggers death of brain tumor cells.
TMZ is often used along with radiation and surgery as part of standard of care for patients with newly diagnosed GBM. It is also used in treating other brain cancers such as anaplastic astrocytoma (AA). Glioblastomas are the most devastating of brain cancers. It is highly invasive making surgical intervention less successful. Even though brain cancers account for a small percentage of all cancers they account for a large number of deaths. Less than 10% of these cases will survive to five years.
Within the last three years, literature reports have shown that aspirin possess anticancer activity and in combination with TMZ may be a promising strategy against malignant glioblastoma. However, to date, we have not found any reports or examples of synthesis and anticancer investigations of hybrid TMZ-aspirin small molecules. Indeed, a theme of our interdisciplinary research collaboration continues to be synthesis and biological activity of small molecule hybrids, in which a single molecular entity is made from component parts that each individually and independently possess therapeutic bioactivity.