Synthesis and Structure Activity Relationships of Novel Dehydroepiandrosterone Derivatives as Potent Neuroprotective Agents and Nitric Oxide Production Inhibitors

Abstract

In this study, a series of dehydroepiandrosterone (DHEA) derivatives were synthesized by linking DHEA with active fragments such as carbamate, phthalimide and indoleacetic acid. In addition, the in vitro neuroprotective effects, via the oxidative stress mechanism, and nitric oxide (NO) production inhibitory activities of each compound were tested. The preliminary structure-activity relationships of them indicated that DHEA with carbamate structure had a certain neuroprotective and anti-inflammatory effect such as 3β-(Cyclohexylamine-1-carboxylate)-5-androsten-17-one (A2) and 3β-(3-Chlorobenzylamine-1-carboxylate)-5-androsten-17-one (A6). And the ester derivatives with indoleacetic acid like 17β–(Heteroauxin-1-carboxylate)-androst-4-en-3-one (A12) also exhibited both significant neuroprotective activity and NO inhibitory activity. According to these results, compound A6 is considered as a potential agent for the treatment of Alzheimer′s disease (AD) and deserve for further investigations.