Date of Graduation

Spring 2016

Document Type

Honors Research Project

Degree Name

Bachelor of Science

Major

Chemistry

Research Sponsor

Dr. Wiley Youngs

First Reader

Dr. Leah Shriver

Second Reader

Dr. Claire Tessier

Abstract

Bis imidazolium salts, with alkyl chain linkers ranging from methylene to dodecyl, were synthesized with naphthylmethyl substituents at the N1 and N1’ positions for a structure-activity relationship (SAR) study. All compounds were characterized by 1H and 13C NMR spectroscopy. The cationic portion of 2 as the PF6 salt, 3, 4, and 5 were also characterized by single-crystal X-ray crystallography. Compounds 1-8, 10, and 12 were tested for their in vitro anti-cancer activity against four NSCLC cell lines via the MTT assay (NCI–H460, NCI–H1975, HCC827, and A549). Compounds 10 and 12 which contained the decyl and dodecyl chains, respectively, had IC50 values of < 1 μM (NCI-H460), < 1 μM (A549), 2 μM (NCI-H1975), and 7 μM (HCC827) and < 1 μM (NCI-H460), < 1 μM (A549), < 1 μM (NCI-H1975), and 4 μM (HCC827), respectively. The results of the MTT assays showed that activity increased as the length of the alkyl linker increased; the bis imidazolium salts with longer chains, compounds 6-8, 10, and 12, had IC50 values comparable to cisplatin.The National Cancer Institute’s (NCI) Developmental Therapeutics Program (DTP) also tested compounds 1-8, 10, and 12 with its 60 human cancer cell line panel in the one-dose assay (10 μM). These results corroborated the SAR findings of our lab that activity increased with the longer chain alkyls, compounds 6-8, 10, and 12, linking the imidazole rings, with compound 12 being the most active having lethality against all of the NSCLC lines examined and lethality against nearly all cell lines tested.

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