Publication: Exploring the chemical space of aromatase inhibitors
Issued Date
2013-11-01
Resource Type
ISSN
1573501X
13811991
13811991
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2-s2.0-84886098173
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Mahidol University
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SCOPUS
Bibliographic Citation
Molecular Diversity. Vol.17, No.4 (2013), 661-677
Suggested Citation
Chanin Nantasenamat, Hao Li, Prasit Mandi, Apilak Worachartcheewan, Teerawat Monnor, Chartchalerm Isarankura-Na-Ayudhya, Virapong Prachayasittikul Exploring the chemical space of aromatase inhibitors. Molecular Diversity. Vol.17, No.4 (2013), 661-677. doi:10.1007/s11030-013-9462-x Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/31169
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Exploring the chemical space of aromatase inhibitors
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Abstract
Aromatase, a rate-limiting enzyme catalyzing the conversion of androgen to estrogen, is overexpressed in human breast cancer tissue. Aromatase inhibitors (AIs) have been used for the treatment of estrogen-dependent breast cancer in post-menopausal women by blocking the biosynthesis of estrogen. The undesirable side effects in current AIs have called for continued pursuit for novel candidates with aromatase inhibitory properties. This study explores the chemical space of all known AIs as a function of their physicochemical properties by means of univariate (i.e., statistical and histogram analysis) and multivariate (i.e., decision tree and principal component analysis) approaches in order to understand the origins of aromatase inhibitory activity. Such a non-redundant set of AIs spans a total of 973 compounds encompassing both steroidal and non-steroidal inhibitors. Substructure analysis of the molecular fragments provided pertinent information on the structural features important for ligands providing high and low aromatase inhibition. Analyses were performed on data sets stratified according to their structural scaffolds (i.e., steroids and non-steroids) and bioactivities (i.e., actives and inactives). These analyses have uncover a set of rules characteristic to active and inactive AIs as well as revealing the constituents giving rise to potent aromatase inhibition. © 2013 Springer Science+Business Media Dordrecht.