Access Type

Open Access Thesis

Date of Award

January 2015

Degree Type

Thesis

Degree Name

M.S.

Department

Chemistry

First Advisor

Jeremy J. Kodanko

Abstract

ABSTRACT

DESIGN AND SYNTHESIS OF ISATIN BASED CASPASE INHIBITORS FOR RUTHENIUM CAGING APPLICATIONS

by

KASUN CHINTHAKA RATNAYAKE

August 2015

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.

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