Molecular Modes of Action of Defensive Secondary Metabolites

Abstract

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.

Isoprenoid Production via Plant Cell Cultures: Biosynthesis, Accumulation and Scaling-Up to Bioreactors

“…To support this idea Eisenreich et al [ 209 ] showed that IPP involved in the biosynthesis of the taxane ring was formed via the MEP pathway. However, other studies [ 28 ] demonstrated the involvement of the cytosolic pathway. A recent study of T. baccata cell cultures showed that while taxol biosynthesis was blocked by the addition of fosmidomycin, an inhibitor of the plastid pathway, it was also reduced by mevinolin, an inhibitor of the cytosolic pathway, indicating that both pathways could be involved [ 210 ].…”

“…In vivo biosynthesis of secondary metabolites is regulated by the plant signalling system and is not crucial for the survival of the individual cells [ 28 ]. In contrast, the auto-selection process in the dedifferentiated cell culture results in preferable production of metabolites that promote intensive and stable proliferation.…”

Peer Review #1 of "The β-carboline alkaloid harmine inhibits telomerase activity of MCF-7 cells by down-regulating hTERT mRNA expression accompanied by an accelerated senescent phenotype (v0.1)"

“…We had shown before that harmine arrested MCF-7 cell growth and induced senescence ( Cytotoxicity can result from an adverse interaction of harmine and other alkaloids with one or more important targets present in a cell including DNA, RNA, or associated enzymes (Roberts & Wink, 1998;Wink & van Wyk, 2008;Wink, 2007). Harmine is known to intercalate DNA and through this it can cause mutations and DNA damage (Wink et al, 1998a;Wink & Schimmer, 2010). Through these interactions cell proliferation can be interrupted or cell death induced (Lansiaux et al, 2002;Möller et al, 2007;Wink, 2007).…”

Antifungal Properties of Bioactive Compounds from Plants

“…Included in this category are such well-known anti-defenses as alkaloids, amines, cyanogenic glycosides, non-protein amino acids, glucosinolates, alkamides and peptides (Wink & Schimmer, 2010). Most nitrogenous secondary metabolites are biosynthesized from common amino acids.…”

“…It´s has studied the secondary metabolites present in various plant species, one to identify its presence, chemical structure and effect on the plant and on other organisms, so that the number of Identified Substances exceed to 100 000 at present (Wink and Schimmer, 2010) Table 2. Distribution of polyphenols compounds on different phylum's in comparative to Plant phylum (Garcia, 2004, as cited in Harborne, 1990 The number of plant species containing one or more of the major groups of compounds with anti-fungal activity is very diverse (Glasby, 1991), in Isolimonene, Isopulegol, Carvone Naigre et al, 1996 5,7-Dihydroxy-4-hydroxyisoflavan, 6,7-Dihydroxy-4_-methoxyisoflavan, 5,7-Dihydroxy-4_- Table 3.…”