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DFT‐based QSAR study and molecular design of AHMA derivatives as potent anticancer agents
Author(s) -
Chen Jincan,
Shen Yong,
Liao Siyan,
Chen Lanmei,
Zheng Kangcheng
Publication year - 2006
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/qua.21285
Subject(s) - quantitative structure–activity relationship , loo , chemistry , steric effects , computational chemistry , homo/lumo , test set , molecular descriptor , substituent , correlation coefficient , density functional theory , outlier , molecule , stereochemistry , mathematics , organic chemistry , statistics
A quantitative structure–activity relationship (QSAR) of 3‐(9‐acridinylamino)‐5‐hydroxymethylaniline (AHMA) derivatives and their alkylcarbamates as potent anticancer agents has been studied using density functional theory (DFT), molecular mechanics (MM+), and statistical methods. In the best established QSAR equation, the energy ( E NL ) of the next lowest unoccupied molecular orbital (NLUMO) and the net charges ( Q FR ) of the first atom of the substituent R , as well as the steric parameter ( MR 2 ) of subsituent R 2 are the main independent factors contributing to the anticancer activity of the compounds. A new scheme determining outliers by “leave‐one‐out” (LOO) cross‐validation coefficient ( q 2 n ‐ i ) was suggested and successfully used. The fitting correlation coefficient ( R 2 ) and the “LOO” cross‐validation coefficient ( q 2 ) values for the training set of 25 compounds are 0.881 and 0.829, respectively. The predicted activities of 5 compounds in the test set using this QSAR model are in good agreement with their experimental values, indicating that this model has excellent predictive ability. Based on the established QSAR equation, 10 new compounds with rather high anticancer activity much greater than that of 34 compounds have been designed and await experimental verification. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2007