Design strategies, chemistry and therapeutic insights of multi-target directed ligands as antidepressant agents

Abstract

: Depression is one of the major disorders of the central nervous system worldwide and causes disability and functional impairment. According to the World Health Organization, around 265 million people worldwide are affected by depression. Currently marketed antidepressant drugs take weeks or even months to show anticipated clinical efficacy but remain ineffective in treating suicidal thoughts and cognitive impairment. Due to its multifactorial complexity, single-target drugs did not always produce satisfactory results and lacks the desired level of therapeutic efficacy. Recent literature reports revealed improved therapeutic potential of multi-target directed ligands due to their synergistic potency and better safety. Medicinal chemists have gone to great extents for the design of multi-target ligands by generating structural hybrids of different key pharmacophores with improved binding affinities and potency towards different receptors or enzymes. This article compiled the design strategies of recently published multi-target directed ligands as antidepressant agents. Their biological evaluation, structural-activity relationships, mechanistic and in silico studies were also described. This article will be highly useful for the researchers to design and develop multi-target ligands as antidepressants with high potency and therapeutic efficacy.