Date of Submission

Spring 2013

Academic Program

Biology

Project Advisor 1

Michael Tibbetts

Abstract/Artist's Statement

The use of organometallic compounds as anticancer drugs has become standard procedure since the discovery of the first platinum-based organometallic compound cisplatin, which remains the most effective platinum drug synthesized. Cisplatin, as well as most organometallic anticancer drugs, achieves its effect against cancer by forming DNA-compound adducts, in which the DNA is distorted in such a fashion as to hinder essential DNA metabolic functions and cause cytotoxicity. The discovery of the effectiveness of ruthenium (III) and the reduction into its active form ruthenium(II) has led to the development of a whole new type of anticancer drugs which don’t necessarily target a cell’s DNA, but instead bind proteins, organelles, and other larger complexes in the cytoplasm of cells. The discovery of the activity of NAMI-A, a ruthenium (III) complex drug in the last few years has shown the possibilities of creating more cancer specific agents that can target metastasis, a previously majorly untreatable reality. AH197 and IT127 are two novel compounds that contain both ruthenium(III) and platinum(II) centers, that are designed to incorporate the previously established properties of the two organometallic anticancer agents, R(III) and Pt(II), into more effective single agents. The goal of this project was to create an effective method by which to observe and quantify the motility of A549 lung cancer cells in comparison to noncancerous immortalized mouse keratinocytes, MK116. Previous research in this lab on the motility of IT127 and AH197 demonstrated in vivo IT127’s ability to outperform cisplatin in hindering cell mobility, and AH197s potential as an anti-metastatic agent shown favorably in comparison to Ru(III) NAMI-A. That research was quantifying the amount of drug needed for complete inhibition of cell movement, where this study is more concerned with the manner in which cells move specifically variables like distance traveled, speed, and type of motion, directed or random. The overall intention of this work is to figure out which compounds are most effective against cell movement.

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