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Quantum chemical and statistical study of megazol‐derived compounds with trypanocidal activity
Author(s) -
Rosselli F. P.,
Albuquerque C. N.,
da Silva A. B. F.
Publication year - 2005
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.20532
Subject(s) - chemistry , homo/lumo , molecular descriptor , quantitative structure–activity relationship , lipophilicity , substituent , computational chemistry , dihedral angle , mulliken population analysis , partition coefficient , principal component analysis , molecule , stereochemistry , density functional theory , mathematics , organic chemistry , hydrogen bond , statistics
In this work we performed a structure–activity relationship (SAR) study with the aim to correlate molecular properties of the megazol compound and 10 of its analogs with the biological activity against Trypanosoma cruzi (trypanocidal or antichagasic activity) presented by these molecules. The biological activity indication was obtained from in vitro tests and the molecular properties (variables or descriptors) were obtained from the optimized chemical structures by using the PM3 semiempirical method. It was calculated ∼80 molecular properties selected among steric, constitutional, electronic, and lipophilicity properties. In order to reduce dimensionality and investigate which subset of variables (descriptors) would be more effective in classifying the compounds studied, according to their degree of trypanocidal activity, we employed statistical methodologies (pattern recognition and classification techniques) such as principal component analysis (PCA), hierarchical cluster analysis (HCA), K‐nearest neighbor (KNN), and discriminant function analysis (DFA). These methods showed that the descriptors molecular mass ( MM ), energy of the second lowest unoccupied molecular orbital ( LUMO+ 1), charge on the first nitrogen at substituent 2 ( qN′ ), dihedral angles ( D 1 and D 2), bond length between atom C4 and its substituent ( L 4), Moriguchi octanol‐partition coefficient ( MLogP ), and length‐to‐breadth ratio ( L/Bw ) were the variables responsible for the separation between active and inactive compounds against T. cruzi . Afterwards, the PCA, KNN, and DFA models built in this work were used to perform trypanocidal activity predictions for eight new megazol analog compounds. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2005