Mmff94x

A dataset of chemical structures and in vitro inhibitory activities of human aromatase inhibitors was compiled following an exhaustive literature search and review. The in vitro activities were measured under similar experimental conditions using human placental microsomes incubated with 1β[³H]-androstenedione. Racemic mixtures and compounds containing highly flexible chain substituents (chain length ≥ 7) were excluded during dataset development resulting in 175 steroidal and 124 aromatic azaheterocyclic AIs. The in vitro activities were expressed as the half maximal inhibitory concentration (IC₅₀) and transformed into corresponding pIC₅₀ [− log(IC₅₀)] as the expression of inhibition potency. The activity among the steroidal and azaheterocyclic AIs covered over three (42–200,000 nM) and four (1–467,000 nM) orders of magnitude for aromatase inhibition, respectively. The AIs in the dataset were protonated and energy minimized with MMFF94x using MOE (Molecular Operating Environment, Chemical Computing Group, Ontario, Canada). The structures, inhibition potencies, and references of the compounds are available in Additional file 1.

Docking for the synthesized compounds (S1–S18) and reference compound indomethacin was performed via their 3D structures and energy was minimized using MMFF94x of Molecular Operating Environment energy minimization module (MOE, Version 2015, Chemical Computing Group Inc., Montreal, Quebec, Canada).3D crystal structure of COX-2 enzyme (PDB ID: 4COX) was selected from Protein Data Bank database (http://www.rcsb.org). The reported protocol was followed for preparing selected 3D structure of COX-2 enzyme for docking. Docking procedure was also followed using the standard protocol implemented in MOE 2015 and the geometry of resulting complexes was studied using the MOE’s Pose Viewer utility.