Synthesis and Biochemical Properties of DNA-Intercalators using Natural Products as Lead Compounds.

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The purpose of our project was the isolation and structural elucidation of novel chemical constituents from Rutaceous plants, and synthetic and biochemical studies of DNA intercalating agents derived from the natural products as lead compounds.1. The following Rutaceous Plants were investigated.: (1) one genus of Glycosmis. (2) Three genera of Murrays. (3) Fourteen genera of Citrus.2. Novel chemical constituents isolated were classified as follow: (1) Acridones. (2) Binary acridones. (3) Homoacridones. (4) Acridone-Coumarin dimers. (5) Carbazoles. (6) Carbazolequinones. (7) Binary carbazoles. (8) Indoles. (9) Coumarins. (10) Binary coumarins. (11) Flavonoids. (12) Others.3. Five 9-substituted 1,3-dimethoxyaminoacridines were syntheized as DNA intercalating agents.4. Twentyfour 5-methoxy-7-methyl-7H-pyrido[4,3-c]carbazoles were synthesized from "mukonal", one of carbazole alkaloids, as a lead compound.5. The mutagenic activities were found to be enhanced by the location of an amino- alkane side chain on the skeleton in Ames tests of these derivatives.6. Among thirty acridone alkaloids, citrusinine-I and atalaphillinine were found to exhibit potent anti-herpesvirus and anti-malarial activities, respectively.7. Spectrometric analyses (UV and NMR) of synthetic pyridocarbazoles showed the presence of strong stacking interactions between these molecule themselves and all kind of DNA-bases.