Synthesis and Anti-Cancer Activity of Benzisoxazolo[2,3-a]azinium Tetrafluoroborates
Poster Number
34
College
College of Arts and Sciences
Department
Chemistry, Physics, Geology, & the Environment
Faculty Mentor
James M. Hanna, Jr., Ph.D. and Takita Sumter, Ph.D.
Abstract
Despite the success of genomics in identifying new essential oncogenic signaling pathways, there have been a limited number of sustainable leads in anticancer drug discovery to address increasing chemoresistance. To improve progress in this area, our lab synthesized several novel benzisoxazoloazinium tetrafluoroborates with structural characteristics similar to clinically effective DNA binding drugs. From a series of eight tricyclic pyridinium compounds with various substituents, a methyl-substituted compound effectively inhibits proliferation in colon cancer cell lines (IC50 = 2.95 micromolar) and shows significant in silico and in vitro DNA binding affinity. Incorporation of a fourth ring generated quinolinium derivatives that recapitulate DNA binding activity of ellipticine. Preliminary IC50 values for these compounds range from 52 to 202 micromolar. To evaluate the impact of a second nitrogen, we synthesized and evaluated a quinoxalinium analog; results for this compound (IC50 of 18 micromolar) show increased cytotoxicity compared to the quinolinium analog. All compounds induce cell death via non-apoptotic pathways. Future work will involve the synthesis and evaluation of other quinoxalinium analogs, as well as evaluation of their activity against PC3 human prostate cancer cells.
Start Date
24-4-2015 3:20 PM
End Date
24-4-2015 4:50 PM
Synthesis and Anti-Cancer Activity of Benzisoxazolo[2,3-a]azinium Tetrafluoroborates
Richardson Ballroom
Despite the success of genomics in identifying new essential oncogenic signaling pathways, there have been a limited number of sustainable leads in anticancer drug discovery to address increasing chemoresistance. To improve progress in this area, our lab synthesized several novel benzisoxazoloazinium tetrafluoroborates with structural characteristics similar to clinically effective DNA binding drugs. From a series of eight tricyclic pyridinium compounds with various substituents, a methyl-substituted compound effectively inhibits proliferation in colon cancer cell lines (IC50 = 2.95 micromolar) and shows significant in silico and in vitro DNA binding affinity. Incorporation of a fourth ring generated quinolinium derivatives that recapitulate DNA binding activity of ellipticine. Preliminary IC50 values for these compounds range from 52 to 202 micromolar. To evaluate the impact of a second nitrogen, we synthesized and evaluated a quinoxalinium analog; results for this compound (IC50 of 18 micromolar) show increased cytotoxicity compared to the quinolinium analog. All compounds induce cell death via non-apoptotic pathways. Future work will involve the synthesis and evaluation of other quinoxalinium analogs, as well as evaluation of their activity against PC3 human prostate cancer cells.
