| dc.description.abstract | Natural products have played and continue to play an invaluable role in the drug discovery process related to all disease types and, in particular, in the areas of cancer and infectious diseases. Over 1000 years the Kallawaya Indians of Bolivia developed an unwritten pharmacopoeia of about 1000 plants which provide potential resources for drug development. Twenty samples of 14 plant species were extracted and tested for anti-HIV, anti-tumor and other biological activities. From an anti-tumor active extract of the plant Satureja boliviana , 10 compounds were isolated and identified by spectroscopic methods. These compounds included three known and one new naturally occurring terpene, 4-acetoxypulegone and six flavonoids. The anti-tumor active compound was 5-hydroxy-6,7,8,4 ? -tetramethoxyflavanone which was synthesized for further animal evaluation and structure comfiramtion. 3,5-Dicaffeoylquinic acid (3,5-DCQA) isolated from another Kallawaya plant was the first compound whose anti-HIV activity was due to inhibition of HIV-integrase. Since coffee beans ( Coffea robusta ) are more readily available source of isomeric DCQA's, they were chosen as sources of additional material for further anti-HIV studies. Therefore a preparative HPLC method was developed to separate the DCQA's. 3,4-DCQA, 4,5-DCQA and 3,5-DCQA were isolated, identified and the complete NMR assignments were made with the aid of 2-D NMR. Both the dicaffeoylquinic acids and the dicaffeoyltartaric acids (DCTA's) are potent and selective inhibitors of both HIV-1 integrase (IN) and HIV-1 replication in tissue culture. In order to probe the structural features responsible for the anti-HIV and HIV-IN inhibitory activity, a series of DCTA analogues were prepared. The structure-activity relationships of those compounds were studied. Finally, the effect of Mn 2+ on the 13 C NMR spectra of quinic acid, 5-DCQA and 3,4-DCQA was studied. | |
