Biological Evaluation of Novel Benzisoxazolo[2,3-a]azinium Tetrafluoroborates as Anticancer Agents
Poster Number
45
College
College of Arts and Sciences
Department
Chemistry, Physics, Geology, & the Environment
Abstract
Ellipticine has been effectively used to treat various types of cancer. This aromatic, planar, antineoplastic drug works primarily by DNA intercalation, and its derivatives represent promising options for cancer drug discovery. DNA intercalators are small molecules that can bind to DNA between base pairs, resulting in the inhibition of replication and providing a viable option for cancer treatment. Several novel benzisoxazolo[2,3-a] pyridinium and quinolinium tetrafluoroborate salts with structural characteristics similar to ellipticine were evaluated and shown to effectively kill colon cancer cells at single-digit micromolar concentrations. Previously, the benzisoxazolo[2,3-a]pyridinium compounds were evaluated as possible anticancer agents, and various R-groups were tested on the structure to come to the conclusion that a methyl substituent is the most successful. To expand on this work, we evaluated the anti-cancer activity of benzisoxazolo[2,3-a]quinolinium tetrafluoroborate compounds bearing methyl substituents in the 1-methyl, 2-methyl, 3-methyl, and 4-methyl positions and tested them against HCT 116 human colon carcinoma cells. Results were analyzed from a mechanistic perspective, and our preliminary data indicate limited survival of colon cancer cells when treated with 50 µM drug. Additionally, the toxicity assays employed demonstrate an inverse correlation between concentration of drug and cell survival. These findings suggest that benzisoxazolo[2,3-a]quinolinium tetrafluoroborates are an effective lead for better understanding molecular cancer pathways; additional studies will be aimed at detailed analysis of the DNA binding mechanism of these compounds and expansion of our drug library.
Honors Thesis Committee
Takita Sumter, Ph.D.; James M. Hanna, Jr., Ph.D.; and Nicholas Grossoehme, Ph.D.
Previously Presented/Performed?
22nd Annual SAEOPP McNair/SSS Scholars Research Conference, Atlanta, Georgia, June 2016
Grant Support?
Supported by grants from the NCI and NIGMS of the National Institutes for Health and the National Science Foundation.
Start Date
21-4-2017 2:15 PM
Biological Evaluation of Novel Benzisoxazolo[2,3-a]azinium Tetrafluoroborates as Anticancer Agents
Richardson Ballroom
Ellipticine has been effectively used to treat various types of cancer. This aromatic, planar, antineoplastic drug works primarily by DNA intercalation, and its derivatives represent promising options for cancer drug discovery. DNA intercalators are small molecules that can bind to DNA between base pairs, resulting in the inhibition of replication and providing a viable option for cancer treatment. Several novel benzisoxazolo[2,3-a] pyridinium and quinolinium tetrafluoroborate salts with structural characteristics similar to ellipticine were evaluated and shown to effectively kill colon cancer cells at single-digit micromolar concentrations. Previously, the benzisoxazolo[2,3-a]pyridinium compounds were evaluated as possible anticancer agents, and various R-groups were tested on the structure to come to the conclusion that a methyl substituent is the most successful. To expand on this work, we evaluated the anti-cancer activity of benzisoxazolo[2,3-a]quinolinium tetrafluoroborate compounds bearing methyl substituents in the 1-methyl, 2-methyl, 3-methyl, and 4-methyl positions and tested them against HCT 116 human colon carcinoma cells. Results were analyzed from a mechanistic perspective, and our preliminary data indicate limited survival of colon cancer cells when treated with 50 µM drug. Additionally, the toxicity assays employed demonstrate an inverse correlation between concentration of drug and cell survival. These findings suggest that benzisoxazolo[2,3-a]quinolinium tetrafluoroborates are an effective lead for better understanding molecular cancer pathways; additional studies will be aimed at detailed analysis of the DNA binding mechanism of these compounds and expansion of our drug library.
