Publication Date

2020

First Advisor

Steven A. Williams

Document Type

Honors Project

Degree Name

Bachelor of Arts

Department

Biochemistry

Keywords

Neurolenin, Lymphatic filariasis, Helminth, Parasite, Coenorhabdtis elegans, Dirofilaria immitis, Drug development

Abstract

Neglected Tropical Diseases are among the most deadly and destructive diseases in the world, afflicting 149 countries and approximately 2 billion people (27% of the world’s population). Although there are many different types of NTDs, none are more widespread and problematic than those caused by parasitic helminths. Approximately 120 million people worldwide are infected with lymphatic filariasis, and a shocking 1.5 billion are infected with Strongyloidiasis, Hookworm Infection, Trichuriasis, and/or Ascariasis. Although each of these diseases poses its own unique challenges, they all share the common characteristic of being derived from parasitic nematodes.

Drug development efforts have been semi-successful with the introduction of diethylcarbamazine (DEC), ivermectin, and albendazole, but these options do not target adult nematodes and are not easy to mass-distribute on a consistent basis due to the excessive amount of doses needed to alleviate an infection. Thus, a prospective drug that does not exclusively target microfilariae would prove useful to drug effectiveness and distribution efforts, as adult nematodes are capable of reproducing and continuing infectious cycles.

Our goal is to test a sesquiterpene lactone derived from the plant Neurolaena lobata, neurolenin B, for its bioactivity against two species of nematode: Caenorhabditis elegans, and Dirofilaria immitis. Findings from previous research have proven the effectiveness of neurolenin B against the filarial parasite Brugia pahangi, which causes lymphatic filariasis in cats and other mammals (a close relative to B. malayi, which causes LF in humans). Thus, because C. elegans is a phylogenetically dissimilar species from its filarial counterpart, bioactivity would allude to a range of target species that may respond to neurolenin B. D. immitis, although more closely related to B. pahangi than C. elegans, would still suggest a promising range of target species if affected.

My research showed that neurolenin B is not at all bioactive against C. elegans, but is significantly bioactive against adult D. immitis. This suggests that although neurolenin B may not be effective against non-filarial nematodes, it is potentially bioactive against a wider range of filarial nematode species than just those that cause lymphatic filariasis. Thus, neurolenin B could theoretically be used to treat other filarial diseases such as onchocerciasis and loiasis.

Rights

©2020 Grace Caroline Wessels. Access limited to the Smith College community and other researchers while on campus. Smith College community members also may access from off-campus using a Smith College log-in. Other off-campus researchers may request a copy through Interlibrary Loan for personal use.

Language

English

Comments

49 pages : illustrations (chiefly color), color map. Includes bibliographical references (pages 44-48)

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