Structure-activity studies, evaluating

Klopman, G. (1984) Artificial intelligence approach to structure-activity studies. Computer automated structure evaluation of biological activity of organic molecules. J. Am. Chem. Soc. 106, 7315-7318. 

Substituent Parameters. A significant advance was made, in the structure-activity studies with the Hill reaction, when Hansch and Deutsch (12) evaluated some of the published Hill inhibition data with a multiple regression analysis, an extra-thermodynamic approach, or the so-called sigma, pi (a, T ) regression analysis. The principle of the approach rests on the assumption that changes in biological activity can be correlated with measurable molecular or substituent parameters. This analysis involved equations of the following type ... 

Klopman G, Srivastava S, Kolossvary I, Eppant RF, Ahmed N, Eppant RM (1992) Structure-activity study and design of multidrug-resistant reversal compounds by a computer automated structure evaluation methodology. Cancer Res 52 4121-4129... 

Klopman, G. (1984). Artificial Intelhgence Approach to Structure-Activities Studies. Computer Automated Structure Evaluation of Biological Activity of Organic Molecules. J.Am. Chem. Soc., 106,7315-7321. 

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. 

Youngster, S.K. Nicklas, W.J. and Heikkila, R.E. Structure-activity study of the mechanism of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity. II. Evaluation of the biological... 

In order to determine the exact mechanism, structure-activity studies were performed OPZ and 5-(4-methoxyphenyl)-3H-l, 2-dithiole-3-thione were shown to be similarly effective on the inhibition of preneoplastic lesions induced by AFBi, while treatment with 1,3-dithiole-2-thione was without effect [31]. The efficacy of OPZ compared to other dithiolethiones was further studied by evaluating the effects of 17 dithiolethiones on acute hepatotoxicity of AFBl in rats [32]. The results demonstrated that, although several dithiolethiones were more active than OPZ in inhibiting toxicity, no structural motif linked to these chemoprevention properties could be identified. 

Activity. Our structure-activity studies involved the evaluation of oxazoles and thiazoles as the central component, aryl and heteroaryl substitution about the azole heterocycle and optimization of substituents on the peripheral aryl/heteroaryl moieties. 

B, Structure-Activity Studies - There is an Increasing tendency to use the newer tests (inflammed foot, writhing, bradykin) for evaluation of analgesic potency but, unless otherwise specified, potency estimates in the following discussion are based on the mouse hot plate assay. 

From a chemical standpoint, the compounds in classes 4fand 4g constitute an extremely difficult problem for structure-activity studies. Some of them, e.g., the pyrrolizidine alkaloids, have been investigated in great detail (Fishbein et al., 1970, and references therein), and their mutagenic and sterilizing activity is well documented. Others, particularly those that were discovered only recently, are still under investigation, and their full biological evaluation will have to await further development. 

Cui, J., Fan, L Huang, Y, Xin, Y, and Zhou, A. (2009) Synthesis and evaluation of some steroidal oximes as cytotoxic agents Structure/ activity studies (11). Steroids, 74,989-995. 

---