Resveratrol-Inspired Synthetic Compounds for Glioblastoma Stem Cell Cytotoxicity
Abstract
Glioblastoma is an aggressive brain tumor that poses a formidable challenge in terms of treatment due to its infiltrative nature and lack of effective conventional therapies. The presence of treatment resistant glioblastoma stem cells (GSCs) is hypothesized to be responsible for tumor growth; therefore, successful elimination of GSCs is necessary to prevent post-therapy tumor recurrence and patient death. Resveratrol (RSV) is a natural polyphenolic stilbene found vastly in plant products, such as the skin of red grapes. RSV and its analogs are known for their antimicrobial, neuroprotective, antiaging, anti-inflammatory, cardioprotective, and blood-sugar lowering properties. A challenge of utilizing RSV in drug treatment is its low systemic bioavailability; however, several studies indicate that key substitutions of certain functional groups on one of the aromatic rings of stilbene optimizes the chemotherapy properties and enhances the aforementioned applications of RSV. Until now, diarylacrylonitrile analogs have not been explored for their cytotoxicity towards GSCs. The objective of this project is to synthesize a series of resveratrol-inspired compounds retaining stilbene moiety and determine their cytotoxic potential toward GSCs. The synthesis was achieved by coupling substituted arylacrylonitriles with aromatic aldehydes by Knoevenagel Condensation. GSC viability in response to compound treatment was determined by MTS assay. Of the 36 compounds synthesized to date, it was observed that arylacrylonitriles coupled with methoxy substituted aromatic aldehydes significantly reduced GSC viability, while nitro-containing compounds appeared to promote cell differentiation. Taken together, these may be promising lead compounds for further development.
Faculty Sponsors
Dr. Regina Graham, Dr. Venkatesh Shanbhag
Project Type
Event
Location
Alvin Sherman Library
Start Date
4-3-2024 12:30 PM
End Date
4-4-2024 1:30 PM
Resveratrol-Inspired Synthetic Compounds for Glioblastoma Stem Cell Cytotoxicity
Alvin Sherman Library
Glioblastoma is an aggressive brain tumor that poses a formidable challenge in terms of treatment due to its infiltrative nature and lack of effective conventional therapies. The presence of treatment resistant glioblastoma stem cells (GSCs) is hypothesized to be responsible for tumor growth; therefore, successful elimination of GSCs is necessary to prevent post-therapy tumor recurrence and patient death. Resveratrol (RSV) is a natural polyphenolic stilbene found vastly in plant products, such as the skin of red grapes. RSV and its analogs are known for their antimicrobial, neuroprotective, antiaging, anti-inflammatory, cardioprotective, and blood-sugar lowering properties. A challenge of utilizing RSV in drug treatment is its low systemic bioavailability; however, several studies indicate that key substitutions of certain functional groups on one of the aromatic rings of stilbene optimizes the chemotherapy properties and enhances the aforementioned applications of RSV. Until now, diarylacrylonitrile analogs have not been explored for their cytotoxicity towards GSCs. The objective of this project is to synthesize a series of resveratrol-inspired compounds retaining stilbene moiety and determine their cytotoxic potential toward GSCs. The synthesis was achieved by coupling substituted arylacrylonitriles with aromatic aldehydes by Knoevenagel Condensation. GSC viability in response to compound treatment was determined by MTS assay. Of the 36 compounds synthesized to date, it was observed that arylacrylonitriles coupled with methoxy substituted aromatic aldehydes significantly reduced GSC viability, while nitro-containing compounds appeared to promote cell differentiation. Taken together, these may be promising lead compounds for further development.
