Antileishmanial Chalcones: Statistical Design, Synthesis, and Three-Dimensional Quantitative Structure−Activity Relationship Analysis
A large number of substituted chalcones have been synthesized and tested for antileishmanial and lymphocyte-suppressing activities. A subset of the chalcones was designed by using statistical methods. 3D-QSAR analyses using 67 (antileishmanial activity) and 63 (lymphocyte-suppressing activity) of th...
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Published in | Journal of medicinal chemistry Vol. 41; no. 24; pp. 4819 - 4832 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
WASHINGTON
American Chemical Society
19.11.1998
Amer Chemical Soc |
Subjects | |
Online Access | Get full text |
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Summary: | A large number of substituted chalcones have been synthesized and tested for antileishmanial and lymphocyte-suppressing activities. A subset of the chalcones was designed by using statistical methods. 3D-QSAR analyses using 67 (antileishmanial activity) and 63 (lymphocyte-suppressing activity) of the compounds for the training sets and 9 compounds as an external validation set were performed by using the GRID/GOLPE methodology. The Smart Region Definition procedure with subsequent region selection as implemented in GOLPE reduced the number of variables to approximately 1300 yielding 3D-QSAR models of high quality (lymphocyte-suppressing model, R 2 = 0.90, Q 2 = 0.80; antileishmanial model, R 2 = 0.73, Q 2 = 0.63). The coefficient plots indicate that steric interactions between the chalcones and the target are of major importance for the potencies of the compounds. A comparison of the coefficient plots for the antileishmanial effect and the lymphocyte-suppressing activity discloses significant differences which should make it possible to design chalcones having a high antileishmanial activity without suppressing the proliferation of lymphocytes. |
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Bibliography: | ark:/67375/TPS-GHFN40ZJ-R istex:47E1EE4EB11BBF1752E88B337C84A964A810D1B1 |
ISSN: | 0022-2623 1520-4804 |
DOI: | 10.1021/jm980410m |