A Promising Drug Candidate as Potent Therapeutic Approach for Neuroinflammation and Its In Silico Justification of Chalcone Congeners: a Comprehensive Review

Multiple genetic, environmental, and immunological variables cause neuropsychiatric disorders (NPDs). The induced inflammatory immune response is also connected to the severity and treatment outcomes of various NPDs. These reactions also significantly impact numerous brain functions such as GABAergic signaling and neurotransmitter synthesis through inflammatory cytokines and chemokines. Chalcones (1,3-diaryl-2-propen-1-ones) and their heterocyclic counterparts are flavonoids with various biological characteristics including anti-inflammatory activity. Several pure chalcones have been clinically authorized or studied in humans. Chalcones are favored for their diagnostic and therapeutic efficacy in neuroinflammation due to their tiny molecular size, easy manufacturing, and flexibility for changes to adjust lipophilicity ideal for BBB penetrability. These compounds reached an acceptable plasma concentration and were well-tolerated in clinical testing. As a result, they are attracting increasing attention from scientists. However, chalcones’ therapeutic potential remains largely untapped. This paper is aimed at highlighting the causes of neuroinflammation, more potent chalcone congeners, their mechanisms of action, and relevant structure–activity relationships. Graphical Abstract