EXAMINATION OF THE ISOSTERE AND BIOISOSTERE SUBSTITUTIONS IN STRUCTURES OF GEMCITABINE, CAPECITABINE, AND PACLITAXEL: THREE AGENTS UTILIZED FOR TREATMENT OF PANCREATIC CANCER

*Ronald Bartzatt

ABSTRACT

This study presents analysis of isosteres and bioisosteres of gemcitabine, capecitabine, and paclitaxel, which are utilized in the clinical treatment of pancreatic cancer. Pancreatic cancer most commonly occurs (90%) in the form of adenocarcinoma (ductal carcinoma). This is an aggressive and difficult form of cancer to treat, with fewer than 50% of patients surviving past five years. Gemcitabine, capecitabine, and paclitaxel have been shown to be effective in clinical treatment, their molecular properties are determined and presented here for comparison. To increase the number of pharmaceutical agents having potential for treatment of this lethal cancer, the isosteres and bioisosteres of these three agents are shown, along with their molecular properties. Isosteric and bioisosteric substitutions within their molecular structures will bring about changes in molecular properties that are also closely associated with favorable drug-likeness. The molecular properties of the isosteric and bioisosteric substituted compounds are presented and statistically analysed to reveal alterations, however subtle, and statistically analysed for comparison. Summary statistics are shown, with one-way ANOVA (analysis of variance) and one-way ANOSIM (analysis of similarities). In addition, the pattern recognition methodology neighbor joining cluster analysis was applied to reveal with high resolution, the underlying numerical relationships of the molecular properties, as well as revealing similarities or dissimilarities of their molecular properties.

Keywords: Pancreatic Cancer, Gemcitabine, Capecitabine, Paclitaxel, Isosteres.