Malaria is a mosquito-borne disease caused by several species of plcismodium protozoa. It is one o f the major killer diseases o f the world, causing 2 million deaths annually. The most dangerous form is caused by Plasmodium falciparum with infections often ending terminally. Attempts to eradicate malaria have failed due to the emergence of drug resistant strains and thus there is a need for novel anti-malarial drugs. Recently an identical aminopeptidase has been isolated from the both the human malarial parasite P. falciparum and the rodent malarial parasites P. berghi and P. chabaudi. It is significantly different in both size and structure to mammalian aminopeptidases and thus provides a prime target for chemotherapeutic intervention. Investigations were directed towards the design and synthesis of novel selective inhibitors of this enzyme. Initially over forty amino acid and dipeptide derivatives with N- and C-terminal modifications were prepared. These included 7V-cinnamoyl, A^S-dinitrobenzoyl, Ntoluene-/?- sulphonyl, N-2-nitrophthaloyl, vV-phenylureido and 7V-chloroacetyl amino acids, amino esters, amino amides and amino alcohols. The design rationale and synthesis of /V-2-hydroxy-2-phenylacetyl, AL2-hydroxy-3-phenylpropionyl, 7V-3-hydroxy-3 - phenylpropionyl and 2-thio-2-phenylacetyl amino acid derivatives are also presented, along with accompanying structure-activity analysis. The compounds were characterized by I.R. and N.M.R. spectroscopy, as well as high resolution M.S. X-ray crystallography was used to elucidate the crystal structures and hydrogen bonding interactions of two of the compounds. All o f the compounds were tested for inhibitory potency in a novel bioassay based on the liberation of fluorescent 7-amino-4-methyl-coumarin from L-leucine-7- amido-4-methyl-coumarin upon enzymatic hydrolysis of the amide bond. Many of the compounds possessed modest enzyme inhibitory potency in the micromolar range [3- nitrocinnamoyl glycine ethyl ester (3c);IC5o=6.6|jM]. Some of the compounds also acted as potent activators of the aminopeptidase [3-nitrophthaloyl-L-leucine methyl ester (10c); activation at concentration of 10(iM=132.8%], The most effective inhibitor was ./V-2-thio-2-phenylacetyl phenethylamide (30) (IC5o~5.2(_iM).