A homologous series of aspirin analogs with varying degrees of hydrophobicity were synthesized via a multi-year course-based research experience in an Organic chemistry 2 lab class at Lawrence Technological University. Studies have shown that aspirin intake not only reduces the risk of developing colon cancer but also results in tumor regression. Aspirin has been found to inhibit the <i>in-vitro</i> growth and proliferation of colorectal cancer cells. Since the mechanism of action is not clear, studying aspirin analogs to establish a structure-activity relationship could be of medicinal interest. Building further on this, the pre-clinical antitumor activity and structure-activity relationship of the synthesized aspirin analogs were studied using cytotoxicity and molecular assays. Three different tumor cell lines [MiaPaCa-2 (pancreatic ductal adenocarcinoma); HCT-116 (colon cancer); Bon-1 (pancreatic neuroendocrine tumors) and HPDE (normal human pancreatic ductal epithelial cell as controls)] will be exposed to increasing concentrations of aspirin as a positive control and selected aspirin analogs for 24, 48 and 72 hrs followed by cell viability analysis using Trypan Blue and MTT assays. The IC<sub>50</sub> of each analog will be calculated and analogs that are most potent will be further characterized for their anti-tumor potential using a wound healing assay (scratch assay) and long-term growth inhibition using a colony formation assay. The mechanism of anti-tumor activity will be analyzed at the molecular level through Western Blotting and RT-PCR. Progress towards the goal of identifying potent new analogs of aspirin that could be used for the treatment of cancer will be presented.

Evaluation of structurally diverse aspirin analogs for anti-cancer activity

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