Synthesis, characterization, and in vitro anti-tumor studies of bis imidazolium salts with alkyl chain linkers and naphthylmethyl substituents

Author

Steven R. Crabtree, The University of AkronFollow

Date of Last Revision

2023-05-02 18:51:27

Major

Chemistry

Degree Name

Bachelor of Science

Date of Expected Graduation

Spring 2016

Abstract

Bis imidazolium salts, with alkyl chain linkers ranging from methylene to dodecyl, were synthesized with naphthylmethyl substituents at the N¹ and N^1’ 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.

Research Sponsor

Dr. Wiley Youngs

First Reader

Dr. Leah Shriver

Second Reader

Dr. Claire Tessier

Recommended Citation

Crabtree, Steven R., "Synthesis, characterization, and in vitro anti-tumor studies of bis imidazolium salts with alkyl chain linkers and naphthylmethyl substituents" (2016). Williams Honors College, Honors Research Projects. 244.
https://ideaexchange.uakron.edu/honors_research_projects/244