Phytochemical discovery of antifeedant, antimicrobial and antimalarial principles

This thesis examines the phytochemical discovery process from temperate and tropical trees. Thirty extracts of wood and bark of hardwood trees from Eastern North America were examined for insect control and antimicrobial activities. Nine of the bark extracts and four of the wood extracts showed significant growth reducing effects against Ostrinia nubilalis at 0.5%, whereas only two bark extracts and one wood extract showed significant antifeedant effect against Sitophilus oryzae at the same concentration. Slower growing tree species were more biologically active than fast growing ones. Isolation of the bioactive compounds in one of the active species, Prunus serotina, showed that naringenin, its derivative 4 ′methoxynaringenin, and eriodictyol were responsible for the antifeedant effects.; Antimicrobial activity of the hardwood trees was also tested against eight strains of bacteria and six strains of fungi. Eighty-six percent of the bark extracts were active against methicillin-sensitive Staphylococcus aureus; 71% against Bacillus subtilus and 79% against Mycobacterium phlei. The bark extract of Juglans cinerea was active against Pseudomonas aeruginosa 187, Salmonella typhiumurium, and Klebsiella pneumoniae. The wood extracts were less active: 72% were active against S. aureus (methicillin-sensitive), 36% against B. subtilus and 43% against M. phlei. Results from antifungal tests indicated that 36% of the extracts were active against at least one fungal strain and that bark extracts were more active than wood extracts. The bark extract from Juglans cinerea had the broadest spectrum of activities against Candida albicans, Saccharomyces cerevisiae, Cryptococcus neoformans, Trichophyton mentagrophytes, Microsporum gypseum, and Aspergillus fumigatus . In general, the extracts were more active against gram-positive bacteria than gram-negative bacteria and against filamentous fungi than yeast-like fungi. The study also demonstrated a correlation between frequency of traditional medicinal use by the First Nations people and antimicrobial activity of extracts indicating that the traditional knowledge encompasses an understanding of aspects of chemical ecology.; Tropical trees have been used as a source of traditional remedies for malaria. Bioassay-guided isolation of active principles of the traditionally used antimalarial plant, Lansium domesticum from Borneo (Indonesia) was undertaken. Six novel triterpenoids were identified and three derivatives were prepared. All nine compounds were tested for in vitro antimalarial activities against chloroquine sensitive (D6) and chloroquine resistant (W2) Plasmodium falciparum clones. Four of these compounds exhibited high activity comparable to quinine. In vivo studies were conducted using mice infected with Plasmodium bergheii in a 4-day suppression test. The results indicated that methyl 15, acetoxylansiolate produced parasitemia clearance level of 50%. It was concluded that the bitter triterpenoids are responsible for the antimalarial activity of Lansium domesticum.; Gedunin from Cedrela odorata (Meliaceae), a potent in vitro antimalarial agent, was also investigated for its in vivo efficacy. When orally administered at 50 mg/kg/day, gedunin was only able to suppress the parasitemia level by 44%. However, at a combination treatment of gedunin and dillapiol (cytochrome P450 inhibitor), the parasitemia clearance increased to 79%. Furthermore, 7-methoxygedunin, a semiderivative stable to degradation by esterases tested at a daily dose of 50 mg/kg...