Research Interests: Christian Preihs

Functionalization and Further Exploration of Texaphyrins: Approaches to Improved Anticancer Agents

Irrespective of the mode of drug administration, drugs principally have to pass through cell membranes to become active in vivo.  Therefore, a wide range of functional groups have been explored in an effort to improve the uptake properties of known or experimental pharmaceutical agents. Therefore, efforts were made to synthesize motexafin gadolinium (MGd; Xcytrin^®) analogs bearing functional groups with bioselectivity properties. MGd localizes and/or is retained in rapidly growing tissues such as cancerous tumors and has recently completed Phase III clinical testing as an agent for treating brain metastases from non-small cell lung cancer. To make and study texaphyrin analogs whose cellular uptake could be modulated via, e.g., changes in external conditions by adding functional groups provides an incentive for the Sessler group.

One such functional group that has attracted attention is the crown ether.  Crown ethers offer the opportunity to vary the overall polarity, and hence potentially improve the biolocalization properties of a putative active agent through coordination of alkali ions and tertiary amines. [1],[2] Efforts are therefore made to synthesize a texaphyrin monomer, dimer and trimer bearing an 18‑crown‑6 moiety as functional group. [3]             The increased presence of cellular free zinc appears to be involved in several human diseases. Since an increase in the level of free zinc is correlated with oxidative stress, the ability of cyclam to form stable complexes with zinc could be a direct benefit to radiotherapy treatment. Hence, attempts are made to synthesize a texaphyrin-cyclam derivative.

[3] Sessler, J. L.; Mody, T. D.; Ramasamy, R.; Sherry, A. D. New. J. Chem. 1992, 16, 541-544.