Pesticides, structure/activity studies

Scherrer, R. A., The treatment of ionizable compounds in quantitative structure-activity studies with special consideration of ion partitioning, in Magee, P. S. Kohn, G. K. Menn, J. J. (eds.), Pesticide Syntheses through Rational Approaches, ACS Symposium Series 225, ACS (American Chemical Society), Washington, DC, 1984, pp. 225-246. 

As mentioned above, the threat of the misuse of nerve agents eontinues. Also, the requirements on agrieultural produetion inerease the use of pestieides and, beeause of this, deaths of agrieultural workers inerease. Due to the faet that there is no universal oxime that could be applied in every situation of nerve agent or pesticide intoxication, the development of new oximes still continues. We hope that in the near future, new more promising candidates will be found, especially if novel techniques and data from structure-activity studies are used as a starting point for the synthesis of new reactivators. 

Thus the stage of plant development, the timing of chemical treatment, and the environment all require consideration in structure-activity studies. When we superimpose genotypic and phenotypic variations upon this complex of variables, it is apparent that plant regulator research and development is considerably more complex and requires more rigorous and critical evaluation criteria than has been customary in pesticide research. However, attention to such detail should promote discovery of useful chemicals which will play a highly significant role in our future efforts to improve food quality and increase crop productivity. 

S. typhimurlum, S. cerevisiae, and unscheduled DNA synthesis In WI-38 cells differ only In carbonyl substituent. These structural and biological relationships Indicate that structure-activIty studies may be useful In defining mechanisms of action of mutagenic or carcinogenic pesticides and potentially In the Identification of hazardous environmental agents. 

If these conclusions are valid they have important implications for the design of tests to evaluate relative toxicity and also for structure/activity theories for example if the relationship between polarity and toxicity is strongly influenced by decay processes then it is important that these are given appropriate consideration in designing candidate compounds. The analysis presented above also gives a strong support for further pharmacodynamic studies of pesticide action... 

For years, we have been studying QSAR (quantitative structure-activity relationship) analyses of pesticides and other bioactive compounds. In many examples, we have found a decisive role of the steric effect in determining the activity variation. In this chapter, applications of various steric constants such as E E°, Vw and STERIMOL parameters to QSAR studies mostly from our own laboratory are reviewed. 

In addition to their potential as antitumor agents, acetogenins have great potential as natural "organic" pesticides (Mikolajczak et al., 1988,1989 McLaughlin et al., 1997). Bullata-cin (1) and trilobacin (3) (see Figure 13.1) were more potent than rotenone, a classic complex I mitochondrial inhibitor, in a structure-activity relationship (SAR) study using yellow fever mosquito (YFM) larvae (He et al., 1997). 

The author originally reviewed three important aspects of semiochemical research that has been discussed in Volume 9. They are as follows (1) determination of structure including the absolute configuration of bioactive natural products, (2) problems of biological homochirality, and (3) study of structure—activity relationships to invent mimics of bioactive small molecules so as to utilize them as pesticides or medicinals. 

The complex activity and selectivity characteristics of substituted trifluoromethanesulfonanilide herbicides were not correctable with single molecular properties (see Table I and Ref. 5). We were particularly interested in determining whether the multiparameter Hansch equation, whose utility and apparent generality has already been substantiated in correlation studies on enzymatic systems (14, 15, 16, 17, 25), drugs and pharmaceuticals (18,19,20,23,24), pesticides (10,21), and plant growth regulators (22), could be used to provide meaningful structure—activity... 

Molecules of similar biochemical activity often show common 3D shape features. Consequently, the characterization of the shapes of formal molecular bodies and the recognition, description, and, ultimately, the numerical evaluation of similarity among molecules are of major importance in modern pharmaceutical research, as well as in pesticide and herbicide chemistry. The analysis of molecular shape is an important component of research aimed at the elucidation of drug-receptor interactions and in studies of quantitative structure-activity relationships in contemporary drug design. 

Univ., China) presented his recent research results entitled Structure-activity relationship of novel sulfonylurea inhibitors on AHAS . H. Matsumoto (Univ. of Tsukuba, Japan) then introduced his study Mode of action of several classes of herbicides causing photooxi dative injury in plants . The second one dealt with insecticides, where X.-H. Qian (East China Univ. of Science and Technology, China) and K. Matsuda (Kinki Univ., Japan) presented their recent findings on chemistry and biochemistry of neonicotinoids. Interchange between Pesticide Science Societies of Korea and Japan was also maintained at a seminar entitled Current and future R D activities in agrochemical area in Korea and Japan . 

First structure-activity relationships relating to crop protection targets were reported by Fisher in 1984 [47]. This study showed that avermectin Bia was somewhat more active then mUbemydn D against Tetranychus urticae, Hdiothis virescens, and Mdoidogyne incognita. As milbemycin D can be viewed as the 22,23-dihydro-13-desoxy derivative of avermectin Bib, this comparison reflects the influence of the disaccharide portion of avermectins on their activity as pesticides. 

T. T. Fujimoto, J. A. Quinn, A. R. Egan, S. H. Shaber, and R. R. Ross, Pesticide Biochem. Physiol., 30,199 (1988). Quantitative Structure-Activity Relationship Studies of the Fungitoxic Properties of Phenethyl 1,2,4-Triazoles. 

It is a fact that "serendipity" still dominates the discovery of an entirely new class of pesticides, especially one with novel mode of action. The reason is simply because our ability to design compounds to affect enzymes, receptors, or other biochemical targets is still very limited. Modem molecular modeling techniques and the computer-aided study of quantitative structure activity relationship are mainly for the optimization of an original lead (A). 

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