Application of Squaric acid to The Preparation of Bioactive Compounds
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Nucleosides and nucleoside analogues exhibit a broad spectrum of biological activities including antiviral, anticancer, antibacterial and antiparasitic activities, which generally result from their ability to inhibit specific enzymes. Nucleoside analogues can interact with cellular enzymes involved in the biosynthesis or degradation of RNA (ribonucleic acid) and/or DNA (deoxyribonucleic acid) or with specific viral enzymes to result in their biological activities and therapeutic effects. In addition, another possible target is their incorporation into DNA/RNA which could affect replication and transcription. They have been beneficial to the development of new pharmaceuticals. Squaric acid and its derivatives have been successfully used as a bioisosteric group in various biomedicinal areas. The aim of this research proposal was to apply squaric acid analogues to the design and synthesis of novel nucleoside analogues. Three squaric acid-based new nucleoside analogues were made starting from dimethyl squarate. The compounds were 4-amino-3-[((1R,3S)-3-hydroxymethyl-4-cyclopentene)-1-amino]-3-cyclobutene-1,2-dione, 4-methoxy-3-[((1R,3S)-3-hydroxymethyl-4-cyclopen tene)-1-amine]-3-cyclobutene-1,2-dione, and 4-hydroxy-3-[((1R,3S)-3-hydroxymethyl-4-cyclopentene)-1-amine]-3-cyclobutene-1,2-dionate, sodium salt. A key step in their synthesis was the reaction of (1R, 4S)-(-)-4-(hydroxymethyl)cyclopent-2-en-1-ylamine with 4-amino-3-methoxy-3-cyclobutene-1,2-dione, or 3,4-dimethoxy-3-cyclobutene-1,2-dione, followed by hydrolysis to give the above compounds. They were sent to the Developmental Therapeutics Program (DTP) of the National Cancer Institute (NCI, USA) to screen and test in vitro for their potential anticancer activity in cellular assays. Little to modest antitumour activity was detected for these compounds. Meanwhile, their cytotocity to HeLa cells was investigated as well. However, no significant effect was observed by these three compounds. Also, these compounds were sent out to the National Institute of Allergy and Infectious Diseases (NIAID, USA) to test their antiviral activity against various viruses. These tests are in progress.
Cite this work
Meijun Lu (2008). Application of Squaric acid to The Preparation of Bioactive Compounds. UWSpace. http://hdl.handle.net/10012/3913