Premium
An alignment‐independent 3D‐QSAR study on series of hydroxamic acid‐based tumor necrosis factor‐α converting enzyme inhibitors
Author(s) -
Alizadeh Ali Akbar,
HamzehMivehroud Maryam,
Sokouti Babak,
Dastmalchi Siavoush
Publication year - 2016
Publication title -
journal of chemometrics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.47
H-Index - 92
eISSN - 1099-128X
pISSN - 0886-9383
DOI - 10.1002/cem.2817
Subject(s) - quantitative structure–activity relationship , chemistry , hydroxamic acid , stereochemistry , enzyme , tumor necrosis factor alpha , hydrogen bond , tumor necrosis factor α , potency , biochemistry , biology , molecule , organic chemistry , immunology , in vitro
Grid‐independent descriptors are extensively used in 3D quantitative structure‐activity relationship (3D‐QSAR) studies. These kinds of descriptors represent the spatial arrangement of the atoms in a 3D fashion. In the current study, we have developed a 3D‐QSAR model for a set of hydroxamic acid‐based derivatives as tumor necrosis factor‐α converting enzyme (TACE) inhibitors. The generated model revealed the importance of some main moieties in the potency of these compounds. Quinolinyl and hydroxamate moieties have the ability to act as hydrogen bond acceptors and hot spot points. On the other hand, phenyl ring can participate in hydrophobic contacts with the receptor. 3D‐QSAR analyses resulted in the partial least squares model of 3 latent variables with internal and external validation yielding q 2 values of 0.66 and 0.73, respectively. The result of the current study can be used in designing of potent TACE inhibitors where inhibition of TACE enzyme is required, such as inflammatory diseases, atherosclerosis, osteoporosis, autoimmune disorders, allograft rejection, and cancer.