Bile acid-arene conjugates : from photoswitchability to cancer cell detection

Abstract

Steroids are a· group of polycyclic bioorganic compounds showing large structural variation developed during the biological evolution to fulfill different functions in living organisms. Bile acids are natural detergents formed via many enzymatic steps from cholesterol and they possess many biologically important functions. A brief review of bile acid chemistry is presented as an introduction to this doctoral thesis, which is an essential part of bile acid research conducted in the organic chemistry laboratory, Department of Chemistry, University of Jyväskylä. This thesis focuses on various human bile acid derivatives. Sixteen structures with porphyrin core bound via alkylammonium amido spacer to bile acids have been synthesized and characterized by 1H and 13C NMR spectroscopy, electrospray ionization time-of-flight mass spectrometry, and elemental analyses. These potential receptors were screened against some biochemically interesting molecules such as nucleotides and saccharides showing high but not very selective binding affinity. Cell biological studies have been made for four cholic acid-porphyrin derivatives, which showed selectivity for saccharide cancer markers and cancer cells, and which can be used for selective ablation of tumors by photodynamic therapy, PDT. Twelve model structures for the above mentioned porphyrine-bile acid receptors with smaller arene/ alkenyl core have been synthesized and characterized. Among them the cis/trans photoisomerization was controlled in two azobenzene derivatives by the hydrophilities of bile acid moieties in protic solvent. In addition, four different bile acid heteroaryl conjugates have been synthesized. The crystal structure of the lithocholic acid - bithiophene conjugate was determined. Many interesting new ideas to transform bile acids to other biologically important steroidal structures have risen in the course of these studies. The more properties and applications of bile acids are discovered, the more challenges and interests they create to the researchers in chemistry, biochemistry, pharmacology, and medicine.