title: Exploring the chemical space of aromatase inhibitors.
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.
authors.affiliation: Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Bangkok,  10700, Thailand, chanin.nan@mahidol.ac.th.
authors.forename: Chanin
authors.initials: C
authors.lastname: Nantasenamat
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.forename: Prasit
authors.initials: P
authors.lastname: Mandi
authors.forename: Apilak
authors.initials: A
authors.lastname: Worachartcheewan
authors.forename: Teerawat
authors.initials: T
authors.lastname: Monnor
authors.forename: Chartchalerm
authors.initials: C
authors.lastname: Isarankura-Na-Ayudhya
authors.forename: Virapong
authors.initials: V
authors.lastname: Prachayasittikul
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry; D047072:Aromatase Inhibitors / Q000737:chemistry*; D016000:Cluster Analysis; D006801:Humans; D008962:Models, Theoretical; D015394:Molecular Structure
chemical_list: D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors