Honors Theses

Date of Award


Document Type

Undergraduate Thesis


Biomolecular Sciences

First Advisor

John Rimoldi

Relational Format



For years, the human immunodeficiency virus type 1 (HIV-1) and malarial parasites have both been prevalent in sub-Saharan Africa. Coinfections of HIV-1 and malaria are common in areas of geographic overlap as both infections seem to increase the severity of the other. HIV-1 treatments have shown to decrease the Plasmodium infections resulting in a lower malarial incidence. HIV-1 protease inhibitors target a crucial step in the life cycle required for viral maturation and have demonstrated a lower level of resistance compared with other therapies. Recent studies have shown the treatment of HIV-1 with protease inhibitors has resulted in inhibitory effects against the Plasmodium falciparum malaria parasite. With growing resistance to current anti-malarial drugs, the need for new compounds is crucial. In an effort to identify the key functional group in protease inhibitors responsible for malaria inhibition, the lopinavir analogs were designed around blocking the HIV-1 activity. The secondary alcohol required for HIV-1 activity was modified in each of the designed compounds in an effort to isolate the malarial inhibition. The compounds were submitted for biological evaluation in a malarial inhibition assay against the chloroquine-sensitive and chloroquine-resistant strains of P. falciparum. The modifications of the secondary alcohol within the protease inhibitor pharmacophore resulted in a decreased potency against the malaria protozoan,demonstrating a need for further research on how the protease inhibitor targets P. falciparum.



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