Design, Synthesis and Antitumor Studies of Novel Thioxanthone Ring System Derivatives

• Main Authors: Liu-Chuan Shih, 施劉佺
• Other Authors: 黃旭山
• Format: Others
• Language: zh-TW
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/80392179561488242301

碩士 === 國防醫學院 === 藥學研究所 === 98 === Several intrinsic tumor suppressor mechanisms have been found in long-lived organisms such as human to combat the oncogenic somatic mutations which usually arise in proliferating stem-cell compartments. Telomere is a specialized nucleoprotein complex of eukaryotic chromosome. Besides, it is one of the anticancer topic with telomerase. Telomerase, acting as a reverse transcriptase, has been identified as a target for cancer drug discovery. In fact, Most human tumors do not only express telomerase but also have very short telomeres, whereas telomerase activity is either reduced or absent in normal tissues, making the inhibition of telomerase an attractive target for cancer therapeutics. In the recent study shown up the inhibition of telomerase which could be achieved with appropriately planar aromatic structure such as anthraquinone derivatives. This inhibition is believed to occur as a result of the stabilization of telomeric DNA by these compounds as folded G-quadruplex structures, which are known to inhibit telomerase activity. In this research, we will design and synthesis a series of thioxanthone ring system derivatives for their antitumor studies including MTT assay and telomerase inhibition assay. Furthermore, we will not only try to figure out the SARs (structure-activity relationships) of this type analogues which are designed pharmacophore as thioxathone, but also discuss their different skeleton and tricyclic ring system between anthraquinone and thioxathone. A potential anticancer agent will be expected by evaluating from the result of bioassay which mention above.