An Overview of Phenylcyclopropylamine Derivatives: Biochemical and Biological Significance and Recent Developments

Abstract trans ‐2‐Phencylcyclopropylamine (2‐ PCPA ), a potent, clinically used antidepressant, affects monoamine neurotransmitter levels by inhibiting the main metabolizing enzymes, monoamine oxidases ( MAO s). However, the antidepressant action of this compound was not fully explained by its effects on MAOs due to its wide variety of biological effects. 2‐ PCPA also affects depression‐associated pathophysiological pathways, and linked with increased levels of trace amines in brain, upregulation of GABA B receptors (where GABA is gamma amino butyric acid), modulation of phospholipid metabolism, and interference with various cytochrome P450 ( CYP ) enzymes. Consequently, despite its adverse effects and limited clinical applicability, 2‐ PCPA has attracted interest as a structural scaffold for the development of mechanism‐based inhibitors of various enzymes, including lysine‐specific demethylase 1 ( LSD 1), which is a possible target for cancer chemotherapy. In the recent years, many reports have appeared in the literature based on 2‐ PCPA scaffold and their potential medicinal implications. This review mainly focuses on the medicinal chemistry aspects including drug design, structure–activity relationships ( SAR ), biological and biochemical properties, and mechanism of actions of 2‐ PCPA and its derivatives. Furthermore, we also highlight recent advance in this area and discuss their future applications for beneficial therapeutic effects.