Ph.D., and PhD. h.c., University of Innsbruch, Austria
Professor Sosnovsky’s interests have been primarily in medicinal chemistry of the following areas.
Syntheses and evaluations of contrast enhancing agents for clinical NMR imaging (MRI) containing aminoxyl radicals and/or paramagnetic ion complexes of transition metals and lanthanides.
Syntheses and biological evaluations in vivo of anticancer drugs belonging to the class of alkylating agents containing aziridine, nitroso and chloroethylnitroso groups as alkylating moieties. These alkylating moieties were linked to various classes of compounds, such as, phosphoric acid derivatives, ureas, crown ethers, amino acids, peptides. Carbohydrates, carbohydrate-amino acid conjugates, and aminoxyl radicals which function as lipophlicity and transport modifiers.
Ideally, alkylating anticancer drugs should, preferentially, permeate the membranes of cancerous cells in order to alkylate and cross-link the DNA of those cell, without affecting the DNA of healthy cells. Unfortunately, in practice, the anticancer agents are not very selective, and hence, highly toxic. In order to have a systematic approach for the development of more effective drugs, a structure-activity relationship was explored, based on the correlation of anticancer activities in vivo and lipophilicities of judiciously selected potential anticancer drugs. On the basis of data generated by these correlations, a design pattern emerged for the syntheses of new anticancer drugs (see figures to right) with predictable higher activities against leukemia tumors than those of clinical drugs.
“In the Search for New Anticancer Drugs. 26. A Comparison of Anticancer Activities of Several TEPA, Thio-TEPA, Seleno-TEPA, and Azetidine Analoga, Including Congeners Containing an Aminoxyl Moiety”, G. Sosnovsky, J. Lukszo, M. Konieczny, K. Purgstaller, and F. Laib, J. Pharm. Sci., 83, 982 (1994).
“In the Search for New Anticancer Drugs. 27. Synthesie and Comparison of Anticancer Activity in Vivo of Amino Acids, Carbohydrates, and Carbohydrate-Amino Acid Conjugates Containing the [N’-(2-Chlorethyl)-N’-nitroamino] Carbonyl Group.”, G. Sosnovsky and C. T. Gnewuch, J. Pharm. Sci., 83, 989 (1994).
“In the Search for New Anticancer Drugs. 28. Synthesis and Evaluation of Highly Active Aminoxyl Labeled Amino Acid Derivatives Containing the [N’-(2-Chlorethyl)-N’-nitroamino] Carbonyl Group.”, G. Sosnovsky, M. Baysal, and E. Erciyas, J. Pharm. Sci., 83, 999 (1994).
“A study of the Favorskii Rearrangement with 3-romo-4-oxo-2,2,6,6-tetramethylpiperdin-1-oxyl”, G. Sosnovsky and Z.W. Cai, J. Org. Chem. 60, 3414 (1995).
“Preparation of an Aminoxyl Analog of the Anticancer Agent Miltefosine”, G. Sosnovsky, J. Lukszo and R.C. Brasch, Z. Naturförsch., 51b, 888 (1996).
“Chemistry and the Process of Color Photography.”, R.D. Theys and G. Sosnovsky, Chem. Rev., 97, 83 (1997)
“In the Search for New Anticancer Drugs. 29. A Study on the Correlation of Lipophilicities, Ionization Constants and Anticancer Activities of Aminoxyl Labeled TEPA Congeners.”, G. Sosnovsky and P. Bell, Life Sciences, 62, 639-648 (1998).