Open Access Thesis
Date of Award
Jeremy J. Kodanko
DESIGN AND SYNTHESIS OF ISATIN BASED CASPASE INHIBITORS FOR RUTHENIUM CAGING APPLICATIONS
KASUN CHINTHAKA RATNAYAKE
Advisor: Jeremy J. Kodanko, Ph.D.
Major: Chemistry (Organic)
Degree: Master of Science
Apoptosis is the energy dependent programmed cell death. Improper function of apoptosis could lead to diseases such as cancers, strokes, Alziemer’s disease. Caspases are the enzymes involved in the later stage of this process. Peptidyl and non-peptidyl caspase inhibitors have been synthesized recently. These non-peptidyl compound classes which consist of pyrrolidinyl-5-sulfo isatins have showed a greater potency against executioner caspases, caspase-3 and -7. According to literature and for further caging studies, two compounds were designed, synthesized and evaluated their inhibition against caspase-3 in this study. The analog in which its N-1 position alkylated with a 4-methyl pyridine moiety (32) showed higher inhibition than the analog in which N-1 was alkylated with cyanoethyl group (33). Thus, compound 32 was selected for further caging studies with ruthenium.
Ratnayake, Kasun Chinthaka, "Design And Synthesis Of Isatin-Based Caspase Inhibitors For Ruthenium Caging Applications" (2015). Wayne State University Theses. 429.