Date Approved

5-23-2023

Embargo Period

5-24-2023

Document Type

Thesis

Degree Name

M.S. Pharmaceutical Sciences

Department

Chemistry and Biochemistry

College

College of Science & Mathematics

Advisor

Amos Mugweru, Ph.D.

Committee Member 1

Subash Jonnalagadda, Ph.D.

Committee Member 2

Kandalam Ramanujachary Ph.D.

Keywords

Analytical Chemistry, Artemisinin, Chromatography, DNA bases, LC/MS TOF, Mass spectroscopy

Subject(s)

Artemisinin

Disciplines

Biochemistry | Chemistry | Pharmacy and Pharmaceutical Sciences

Abstract

Artemisinin (ART) is a sesquiterpene lactone and a popular malaria drug with potential anticancer properties. In this work, LC/TOF MS was used to investigate the reaction of ART with DNA bases and estradiol. ART-deoxyadenosine and ART-deoxycytidine interactions were studied in the presence of Fe (II) ions. ART-deoxyadenosine and ART-deoxycytidine reaction mixtures gave chromatographic signatures that remained unchanged at room temperature but grew after incubation at 37°C. The change in temperature from room temperature to 37°C was the main driver of adduct formation in these reactions. ART was found to react with Fe (II) ions as observed from several new chromatographic peaks. ART-deoxyadenosine as well as ART-deoxycytidine in the presence of Fe (II) ions resulted in the formation of new chromatographic signatures of adducts consisting of DNA bases and ART. It was clear that the addition of Fe (II) to DNA base-ART mixtures gave rise to new reaction products mediated by a different reaction mechanism. Artemisinin-estradiol reactions were studied in the presence of Fe (II) ions. Artemisinin-estradiol reaction mixtures gave chromatographic signatures that remained unchanged at room temperature but grew after incubation at 37oC. Artemisinin-estradiol in the presence of Fe (II) ions resulted in new chromatographic signatures of adducts of estradiol with artemisinin. It was clear that the addition of Fe (II) to estradiol-artemisinin mixtures gave rise to new reaction products mediated by a different mechanism. Studies of ART reactions with DNA and estradiol in vitro are key in elucidating the elusive mechanism of this drug.

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