MODES OF ACTION OF ALLELOCHEMICAL ALKALOIDS - INTERACTION WITH NEURORECEPTORS, DNA, AND OTHER MOLECULAR TARGETS

Several alkaloids are toxic to insects and vertebrates and, in additio n, can inhibit the growth of bacteria and plant seedlings. In vitro as says were established to elucidate their modes of action and to unders tand their allelochemical properties. Basic molecular targets studied, present in all cells, included DNA intercalation, protein biosynthesi s, and membrane stability. The degree of DNA intercalation was positiv ely correlated with inhibition of DNA polymerase I, reverse transcript ase, and translation at the molecular level and with toxicity against insects and vertebrates at an organismic level. Inhibition of protein biosynthesis was positively correlated with animal toxicity. Molecular targets studied, present only in animals, included neuroreceptors (al pha(1), alpha(2), serotonin, muscarinic, and nicotinic acetylcholine r eceptors) and enzymes related to acetylcholine (acetylcholine esterase and choline acetyltransferase). The degree of binding of alkaloids to adrenergic, serotonin, and muscarinic acetylcholine receptors was pos itively correlated in G-protein-coupled receptors. Receptor binding an d toxicity was correlated in insects. The biochemical properties of al kaloids are discussed. It is postulated that their structures were sha ped in a process termed ''evolutionary molecular modeling'' to interac t with a single and, more often, with several molecular targets at the same time. Many alkaloids are compounds with a broad activity spectru m that apparently have evolved as ''multipurpose'' defense compounds. The evolution of allelochemicals affecting more than one target could be a strategy to counteract adaptations by specialists and to help fig ht off different groups of enemies.