Date of Award

2024

Type

Thesis

Major

Biology

Degree Type

Bachelor of Science

Department

Biology

First Advisor

Dr. Monica Frazier

Second Advisor

Dr. Kerri Taylor

Third Advisor

Dr. Cindy Ticknor

Abstract

Lung cancer is the leading cause of cancer deaths worldwide. The battle against this disease continues to challenge physicians and scientists daily, due to its various forms, treatments, and responses. Depending on the grade and stage of the disease, treatments can be extensive, encompassing surgery, chemotherapy, and radiation therapy. Though these therapeutics can prolong a patient’s life, they often have significant ramifications. For instance, radiation therapy has an extensive list of side effects, from organ damage to loss of fertility. These outcomes have driven scientists to explore the applicability of novel cancer treatments. Imidazolium and benzimidazolium salts have been shown to have anticancer activity 1-4. These compounds, when designed with various substituent properties, specifically hydrophilicity properties, have been shown to have therapeutic tendencies. Moreover, present structure activity relationship (SAR) studies display a correlation in the carbon content versus cytotoxic effect. This SAR research is an exploratory project on the biological activity of the salts, Dibenzyl-benzotriazole (BT 1-1), Bis(2-Naph) Benzotriazole (BT 2-2), 2-Naph QuinBenzotriazole (BT 2-3), Bis-Naphthylacylbenzotriazole (BT 4-4), BisNaphAcyl - 1,2,3-triazole (T3 4-4) and Bis-3-phenylbenzyl-1,2,3- triazole (T3 5-5), on normal lung cells (WI-38), and lung cancer cells (NCI-H1299). This research investigated the biological effects of these salts on the proliferation of both normal (WI- 38) and cancerous (NCI-H1299) lung cells. Both cells were grown to 80% confluency and plated at 5x104 cells/mL. Cells were then treated with 0, 1, 5, 15 and 30 μM of BT 1-1, BT 2-2, BT 2-3 for 48 hours and, BT 4-4, T3 4-4 and T3 5-5 for 72 hours at 37°C in a 5% CO2 incubator. Tamoxifen was used as an internal control at a concentration of 1mM and was shown to negatively affect proliferation as cells maintained an average proliferation rate of about 13% in both cell types. Results of the MTS assay showed that overall, all compounds exhibited a dose-dependent decrease in proliferation of both WI-38 normal and NCI-H1299 cancerous lung cells, with the exception of BT 4-4 at low concentrations. The variability in the proliferation of WI-38 and NCI-H1299 lung cells treated with each compound appeared to be associated with carbon content and hydrophilicity. Specifically, these results follow a similar pattern in that increased carbon content of the benzene on benzotriazolium salts (BT 2-2) exhibit a greater dose-dependent decrease in the proliferation of both normal and lung cancer cells. Studies with the T3 compounds, specifically T3 4-4, which has a smaller carbon core but similar large carbon content, like BT 4-4, show a dose-dependent decrease in proliferation in both WI-38 and NCIH1299 cells. The biological activities of these structurally related compounds are highly important, as it provides insight into those structural differences that are likely to inhibit the proliferation of cancer cells with little effect on normal cells.

Included in

Biology Commons

Share

COinS