Event Title

Biological Evaluation of Novel Benzisoxazolo[2,3-a]azinium Tetrafluoroborates as Anticancer Agents

Poster Number

45

College

College of Arts and Sciences

Department

Department of Chemistry, Physics, and Geology

Honors Thesis Committee

Takita Sumter, Ph.D.; James M. Hanna, Jr., Ph.D.; and Nicholas Grossoehme, Ph.D.

Location

Richardson Ballroom

Start Date

21-4-2017 2:15 PM

Description

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.

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.

Comments

McNair Scholar

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Apr 21st, 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.