The Nonpeptide Low Molecular Mass Toxins from Spider Venoms

Spiders occupy most of the ecological niches of the planet, revealing a huge adaptive plasticity, reflected in the chemical diversity of their venom toxins. The spiders are distributed throughout the planet, adapting themselves to many different environments, to form the largest taxonomic group of organisms with a diet exclusively carnivorous. The organic low-molecular-mass compounds present in spider venoms are used both for defensive purposes and to paralyze/kill their preys. Among the low-molecular-mass organic compounds present in spider venoms, the most common ones are free organic acids, amino acids, biogenic amines, and neurotransmitters. These compounds were also used in the course of evolution as substrates for the biosynthesis of novel spider toxins, which were neglected by the toxinology during a long time, mainly due to the difficulties to isolate and to assign the chemical structures of very low abundant compounds. However, the recent technological advances in the spectroscopic techniques used for structural analysis of small molecules allowed the structural elucidation of many of these toxins in spider venoms, permitting the identification of at least six families of low-molecular-mass toxins in spider venoms: (i) acylpolyamines, (ii) nucleoside analogs, (iii) bis(agmatine)oxalamide, (iv) the betacarboline alkaloids, (v) organometallic diazenaryl compounds, and (vi) dioxopiperidinic analogs. Investigations of structure/activity relationship of these toxins revealed that some of them have been identified both as interesting tools for chemical investigations in neurobiology and as potential models for the rational development of novel drugs for neurotherapeutic uses, as well as for developing specific insecticides.