Antineoplastic agents

Cancer is the second leading cause of death in the western world. In order to treat various types of cancer, platinum-based drugs are most widely employed as metal-containing chemotherapeutic agents. However, their clinical usage is hindered by toxic side effects, and by the emergence of drug resistance. Our focus was to replace platinum with less toxic metal like tin which can give better alternatives for cancer treatment. The major aim of our study was to synthesize novel organotin polyethers (Sn-O) which can be used to combat cancer. Preliminary results from our laboratory using organotin polyethers, that were synthesized by varying the structure of diols showed growth inhibition in Balb-3T3 cells. This study directly led us to hypothesize the two structural windows, first by changing the distance between diol and second, by presence of unsaturation in diols, the biological activity of organotin polyethers (Sn-O) can be enhanced significantly. Different series of polymeric compounds were synthesized based upon these two structural windows and the formation of products was validated using standard techniques like infrared spectroscopy (IR), light scattering photometer, matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) and nuclear magnetic resonance (NMR). The synthesized polymers arrested the growth of cancer cell lines including bone, prostate, colon, breast, pancreas and lung cancer derived cell lines in vitro. In number of instances where chemotherapeutic index values of two and greater were found that these polymers are significantly more active against cancer cells than non-cancerous cells in culture.

Dichloroacetate (DCA) is a chemical with potential to be a cancer therapy due to its ability to treat mitochondrial metabolic disorders. Previous studies have affirmed DCA's ability to target cancer cells, leaving healthy cells unharmed (Bonnet et al., 2007). Javonia Washington continued research that Bonnet et al. began by testing DCA's effectson a greater number of cell types (Washington, 2008). This project collects and analyzes the data generated by Washington's research using the computer programs Excel and SPSS. The analysis shows that DCA concentration is vital when considering the chemical as an anti-cancer drug ; it had a significant effect on the cancerous cells from 0.5mM and higher, but both cancerous and non-cancerous cells died at similar rates when the concentration reached 10mM. Further, DCA affects some cancer cells more quickly than others, which could increase the risk of harming surrounding healthy cells if used improperly as a cancer treatment.

Anticancer drugs, including nocodazole and vinblastine, work by disrupting the dynamics of microtubules. Unfortunately, these drugs often produce numerous side effects, including nausea, vomiting, loss of appetite, loss of hair, increased chance of infection, and fatigue. My thesis research evaluated the efficacy of using repeated low doses of microtubule drugs instead of a single high dose, in an attempt to minimize side effects. Using nocodazole and vinblastine, I first established the minimum effective concentration that disrupts the microtubules in normal human cells grown in vitro and treated cells with those concentrations over a period of several days. I found that microtubules were increasingly depolymerized as the days progressed. Next, I tested a combination of nocodazole and vinblastine at low concentrations.