Date of Degree

5-2024

Document Type

Thesis

Degree Name

Master of Science (MS)

Program

Pharmaceutical Sciences

Advisor

Paulo B. Carvalho

Advisor

Raghunandan Yendapally

Advisor

April L. Risinger

Abstract

Malaria, a life-threatening global health concern, is primarily targeted by mainstream treatments such as artemisinin-based combination therapies, focusing on the blood stage of the disease. Primaquine, one of the few drugs active against the liver stage, faces challenges with reports of resistance in Plasmodium vivax strains and relapsing infections. With the scarcity of liver-stage-targeting drugs and increasing cases of drug-resistant malaria, the World Health Organization emphasizes the urgent need for novel therapeutic agents. Marine organisms are a rich source of new bioactive compounds, and extracts from the Antarctic Sea sponge Inflatella coelosphaeroides revealed new N-methylated peptides exhibiting promising antimalarial activity, targeting both liver (Friomaramide A) and blood stages (Shagamides A, C, and D). These unique N-methylated peptides provide a potential scaffold for antimalarial candidates. Shagamide A, with its simple yet remarkably active structure, is an ideal candidate for future structure-activity relationship studies. Our objective is to develop a synthetic route for Shagamide A, confirming its reported structure. This route will not only validate the compound's structure but also facilitates the future production of analogues. These analogues aim to enhance Shagamide A's biological activity, contributing to the development of potentially more effective antimalarial treatments.

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