Directed C–H activation of 13α-estrone: a pathway to promising AKR1C inhibitors via docking and biological studies

molecular docking, we postulated the binding conformations of active pyridyloxy derivative (6a), triazinyl derivative (7) and aryl carbamate (4) within the AKR1C2 binding site, with all of them showing key interactions with Trp86, Val128, Ile129 and Trp227. The AKR1C2 inhibitors identified in this study represent promising starting points for the development of novel therapeutic agents, limiting metastatic dissemination, particularly in certain aggressive tumor types. Given that AKR1C1-3 isoenzymes often catalyze overlapping biochemical transformations, inhibition of one member may be compensated by another. Thus, while selective AKR1C inhibitors remain valuable, the development of pan-inhibitors also represents a promising therapeutic strategy.