Secondary metabolites (SM) have been shaped by evolution for more than 500 million years. As a result, many of them have distinctive biochemical and pharmacological properties. The molecular modes of action of the main groups of SM are reviewed in this chapter. Details are given on interactions of SM with proteins that can induce conformational changes and thus a modification of their bioactivity. The fluidity and permeability of biomembranes constitute another important target, which is influenced by many lipophilic and amphiphilic SM. A number of SM can either alkylate or intercalate DNA, which can cause mutations and in consequence cancer or malformations. Many SM are cytotoxic because they interfere with biomembranes, proteins of the cytoskeleton or DNA; they often induce programmed cell death (apoptosis). A large number of SM, especially alkaloids modulate neuronal signal transduction by interfering with ion channels, ion pumps, neuroreceptors, choline esterase, monoamine oxidase and other enzymes related to signal transduction pathways. A typical feature of SM is their ability to modulate more than one molecular target; thus, additive and even synergistic activities can be expected.
Two methoxylated xanthone derivatives, eustomin and demethyleustomin, were isolated from the aerial parts of Centaurium erythraea Rafn. Both compounds were identified by spectral analysis. They showed strong antimutagenic properties in Salmonella typhimurium strains TA98, TA100, and TA102, when tested against 2-nitrofluorene, 2-aminoanthracene, ethyl methanesulfonate, and nalidixic acid. The bioantimutagenic character of the compounds was supported by the strong effects shown in post-treatment experiments as well as by results obtained with rec A- mutants of E. coli and Bacillus subtilis. From this it follows that the xanthone derivatives probably interfere mainly with the process of post-replication repair.
The sections in this article areIntroductionInterference of Secondary Metabolites with Neuronal SignallingInterference of Secondary Metabolites withDNAand Related TargetsInterference with Molecular Targets Other than those Related to Neurotransmission orDNAAccumulation of Allelochemicals in PlantsAnimal Responses: Detoxification Mechanisms and AdaptationsConcluding Remarks
Mutagenicity testing of a commercial extract from Rutae Herba (Tinctura Rutae) revealed a strong effect in Salmonella typhimurium strain TA98 without S9 mix. In the presence of S9 mix only a weak response was observed. Moderate mutagenic effects were detected with and without S9 mix using strain TA100. The extract used contained the furoquinoline alkaloids dictamnine, gamma-fagarine, skimmianine, pteleine and kokusaginine, as indicated by g.c. and g.c.-m.s. analysis. The pure compounds exhibited a mutagenic activity only in the presence of S9 mix in strain TA98 as well as in strain TA100, but their specific mutagenicity differed greatly in strain TA98. We conclude that the extract studied contains different mutagenic activities and that these are only partially due to the furoquinolines present in the extract.
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