Plant-derived insecticidal compounds

The potent tetranortriterpenoki limonoids of A. indica (neem) and M. azedarach (chinaberry) (i.e., meliacins) are considered to be among the most promising and interesting of the plant-derived insecticidal compounds yet discovered (17). Azadirachtin (Figure 2) is considered to be the prototype compound for this class of feeding deterrent (antifeedant) and insecticidal substances (17.18.28-31 k... 

Plant-derived insecticides, 14 338-339 Plant-derived secondary compounds, 13 357... 

Several nerve toxins produced by plants are interesting because of their insecticidal properties. Insecticidal nicotine is extracted from tobacco. Rotenone (Figure 19.2) is synthesized by almost 70 legumes. This insecticidal compound is safe for most mammals, with the notable exception of swine. The most significant insecticidal plant derivatives, however, are the pyrethrins, discussed below. 

Plant derived pharmaceuticals are estimated to have an annual value of 9 billion in the U.S. alone (4). Flavors and fragrances have a current worldwide market of about 1.5 billion. Market data for insecticides and other fine chemicals such as pigments are not readily available. The first example, and the only current commercial process based on plant cell culture, is for the production of shikonin in Japan. This compound is both used in medicine and as a pigment (5-7. ... 

Neurotransmitters are removed by translocation into vesicles or destroyed in enzyme-catalysed reactions. Acetylcholine must be removed from the synaptic cleft to permit repolarization and relaxation. A high affinity acetylcholinesterase (AChE) (the true or specific AChE) catalyses the hydrolysis of acetylcholine to acetate and choline. A plasma AChE (pseudo-AChE or non-specific AChE) also hydrolyses acetylcholine. A variety of plant-derived substances inhibit AChE and there is considerable interest in AChE inhibitors as potential therapies for cognition enhancement and for Alzheimer s disease. Organophosphorous compounds alkylate an active site serine on AChE and the AChE inhibition by this mechanism is the basis for the use of such compounds as insecticides (and unfortunately also as chemical warfare agents). Other synthetics with insecticidal and medical applications carbamoylate and thus inactivate AChE (Table 6.4). 

Pesticides are chemicals or biological substances used to kill or control pests. They fall into three major classes insecticides, fungicides, and herbicides (or weed killers). There are also rodenticides (for control of vertebrate pests), nematicides (to kill eelworms, etc.), molluscicides (to kill slugs and snails), and acaricides (to kill mites). These chemicals are typically manmade synthetic organic compounds, but there are exceptions which occur naturally that are plant derivatives or naturally occurring inorganic minerals. 

A unique role is played by chemical communication in the interactions between plants and insects. About half a million insect species feed on plants. The process of reproduction in many plant species is critically dependent upon pollination by insects. It is not surprising, then, to find among the numerous natural products of plants both attractants for useful insects and repellents or even insecticides for plant-eating insects. The remarkable diversity of the these compounds (the list includes acyclic and polycyclic compounds, isoprenoids, aromatic derivatives, heterocyclic compounds, etc.) illustrates the non-selectivity in the structure of the chemical mediators for biological applications. The intimate mechanism of their action is, unfortunately, still insufficiently understood. 

Isobutylamides are a subclass of alkamides based on the amine group 2-methylpropyl. They first aroused the interest of researchers for their insecticidal activities, being toxic to numerous classes of insects including the ubiquitous housefly and mosquito. Upon further investigation, it was obvious the most active insecticidal compounds were the ones that produced the most potent sialagogue (stimulating saliva flow) effects in humans (Brinker 1991/92). Isobutylamides so far investigated are derived from four plant families—Asteracea, Rutaceae, Piperaceae and Aristolochiaceae (see Table 8.3). 

Pyrethrins are a group of closely related, naturally occurring compounds that are the active insecticidal ingredient of pyrethmm and have been used for centuries. Pyrethmm, which has been used as a pesticide in commercial applications since the early nineteenth century, is extracted from the flowers of Chrysanthemum cinerariaefolium and Chrysanthemum cineum [1]. Most of the insecticides derived from plants traditionally have been considered safe for use on animals, and pyrethmm is an example of such material. There are six active insecticidal compounds that comprise the natural pyrethrins pyrethrin 1 and 11, cinerin 1 and 11, and... 

Several of the top 20 pharmaceuticals in gross sales in 1992 were natural products or close derivatives thereof (eg. Mevacor, Ceclor). Of the top 20 crop chemicals in this same period, only one class of compounds, the pyrethroids, are based on a natural substance, the plant metabolite pyrethrin. Three active areas of chemistry have the potential to impact this situation within the next ten years the methoxyacrylate family of fungicides based upon the fungal metabolite, strobilurin Basta, a post-emergent broad-spectrum herbicide based upon the Streptomyces viridochromogenes metabolite phosphinothricylalanylalanine and avermectin, and its semi-synthetic derivatives, insecticides originating from Streptomyces avermitilis. 

Amidases can be found in all kinds of organisms, including insects and plants [24], The distinct activities of these enzymes in different organisms can be exploited for the development of selective insecticides and herbicides that exhibit minimal toxicity for mammals. Thus, the low toxicity in mammals of the malathion derivative dimethoate (4.44) can be attributed to a specific metabolic route that transforms this compound into the nontoxic acid (4.45) [25-27]. However, there are cases in which toxicity is not species-selective. Indeed, in the preparation of these organophosphates, some contaminants that are inhibitors of mammalian carboxylesterase/am-idase may be present [28]. Sometimes the compound itself, and not simply one of its impurities, is toxic. For example, an insecticide such as phos-phamidon (4.46) cannot be detoxified by deamination since it is an amidase inhibitor [24],... 

A series of structurally similar compounds derived by acetate extension of phenylpropanoid precursors is also found in the Piperaceae. Pipercide from Piper nigrum (Piperaceae) was insecticidal, but the mixture of amides from this plant was significantly more toxic and it appears that co-occurring compounds exert synergistic effects (120). 

More recently, a new class of insecticides derived from naphthoquinones found in the South American alpine plant Calceolaria andina has entered development. Compounds are being developed jointly through the British Technology Group (BTG) (following the discovery at Rothamsted Experimental Station) and by Bayer. The mode of action of these compounds is believed to be an inhibition of respiration at site... 

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