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Design And Synthesis Of Novel Chloroquine-Based Antimalarials, Kevin Vincent Murphy

Dissertations and Theses

Malaria is an infectious, often fatal disease that afflicts nearly 200 million people every year. The disease, characterized by recurring and extreme flu-like symptoms, is caused by the protozoan parasite Plasmodium falciparum. Victims usually contract the disease through a mosquito vector. Chloroquine is a chemotherapeutic that was introduced in the 1940s. For many years the drug was the foremost treatment of malaria, being effective and producing few side effects. Unfortunately, tolerance to chloroquine developed when the parasite evolved a resistance mechanism. Newer drugs have been developed and implemented, but these medicines also show a decreasing effect with continued administration. …

Lead Discovery And Optimization Strategies Towards The Development Of 4(1h)-Quinolones And 1,2,3,4-Tetrahydroacridone Analogs With Antimalarial Activity, Richard Matthew Cross

USF Tampa Graduate Theses and Dissertations

The goal of our research endeavor was to successfully employ modern lead discovery and optimization strategies towards the development and identification of compounds possessing antimalarial activity. Preliminary data from in vitro screening at the Walter Reed Army Institute of Research identified several chemotypes including 4(1H)-quinolones and 1,2,3,4-tetrahydroacridones to have potent antimalarial activities. Multiple synthetic routes were devised and implemented which enabled the rapid preparation and isolation of over 400 structurally diverse 4(1H)-quinolones and 1,2,3,4-tetrahydroacridones.

Our research towards discovering and optimizing antimalarials was inspired from the severe impact malaria has had on our planet especially on impoverished countries. There are over …

Design And Synthesis Of Antimalarial Drugs Based On A Chloroquine Scaffold, Steven James Burgess

Dissertations and Theses

There are between 350 and 500 million clinical cases of malaria each year, and over 1 million deaths, with pregnant women and children under the age of 5 being most at risk. Chloroquine (CQ) became the preferred drug to treat malaria in the late 1940s, but is now rendered mostly ineffective in many parts of the world, due to widespread CQ resistance by the malaria parasite. All other malaria treatments suffer from some drawbacks, which include development of resistance, side effects including toxicity, risk for pregnant women and young children, and high cost. Some existing, non-antimalarial, drugs have been found …

Xanthones As Antimalarial Agents : Binding Interactions Between Heme Analogues And Xanthones, Jane Xu Kelly

Dissertations and Theses

Human falciparum malaria is caused by Plasmodium falciparum parasite, which digests host hemoglobin within its food vacuole, releasing toxic heme. P. falciparum detoxifies free heme to hemozoin by polymerization. This process is believed to be the target of most successful antimalarial drugs, chloroquine and quinine, which are now losing their effectiveness due to the spread of multi-drug resistant strains. Xanthones were recognized in the laboratory of Dr. M. Riscoe (Portland VA Medical Center) to bind to heme, preventing heme polymerization [Ignatushchenko, M., Winter R., and Riscoe, M. (1997) FEBS Letters 409, 67].

This thesis reports a study of the interactions …

The Synthesis Of Some Potential Antimalarials : The 3-(4- Choloropheny1) -5, 7- Dichloronaphthylaminoalcohols, Dwight Allen Shamblee

Master's Theses

A new scheme is presented for the preparation of 3~(4-chlorophenyl)-5,7-dichloro-l-methylnaphthalene, from which, four derivatives, 3~(4-chlorophenyl)-~-di(n-butyl)aminomethyl~5,7-dichloro-l-naphthalene-methanol hydrochloride, 3-(4-chlorophenyl)-5,7-dichloro-~-(2-piperidyl)-1-naphthalenemethanol acetate, l-[3-(4-chlorophenyl)-5,77dichloro-lnaphthyl]-3-di(n-butyl)aminopropanol hydrochloride, and 1-[3-(4-chlorophenyl)-5, 7-dichloro-l-naph,thyl]-2-(2-piperidyl) ethanol hydrochloride, were prepared. These four derivatives were submitted to Walter Reed Army Institute of Research for. the determination of their potential as antimalarial agents.

Substituted ℓ-Dialkylaminomethyl-3-Phenyl-1-Naphthalenemethanols, Richard Elroy Davis

Master's Theses

Malaria is still a world health problem. Established antimalarial drugs have become ineffective in many areas because of the emergence of resistant strains of malaria. New efforts have been initiated to study variations of new untried compounds and earlier structures shown to have activity. The 4-quinolinemethanols fall into the latter class. The great activity of the 4-quinolinemethanols is offset by their phytotoxic activity.

The possibility that substituted o(-dialkylaminomethyl-3-phenyl-1- naphthalenemethanols, as analogs of the 4-quinolinemethanols, would be effective antimalarials, yet not have the phototoxic side effect, is discussed in this paper. Synthetic pathways to the naphthalenemhethanols are discussed. Experimental procedures are …