Chalcone: A new scaffold for the development of anti-epileptic medications

Flavonoids chalcones are a highly attended subclass of flavonoids having structural features and a β-unsaturated carbonyl system which have been identified to have the C band in the purine binding region and are promising molecules in the synthesis of new AEDs. Seizure disorder which presents as epilepsy – an episode of neurological dysfunction described by recurrent seizures – is still a major public health issue, especially in LMICs due to inadequate access to antiseizure medication. Even with the newly developed anti-seizure drugs and novel surgical approaches, nearly 30% of patients continue to be pharmacological treatment resistant thus the development of new pharmacological therapies. This review discusses the structural flexibility and pharmacological application of chalcones to overcome the drawbacks associated with first-generation AEDs. Exploring the possibility of altering chalcones’ Functional Selectivity Profile for GABA receptors, as well as imp/map targets along with sodium and calcium channels could potentially lead to the development of a rational therapeutic strategy for drug-resistant epilepsy. Some investigators have also shown that certain chalcone derivatives have substantial anticonvulsant effects, better therapeutic profiles, and lesser harmful effects than standard AEDs. The superior formation of chalcones through microwave-assisted and green chemistry also supports the various strategies for fouling chalcones with improved therapeutic promise and bioavailability. It also provides information regarding the ability of chalcones as multi-target directed drugs, structure-activity relationships, and some issues related to the regulation of chalcones for clinical use. Despite being switchable phase II enzymes that possess diverse multi-parametric action potentials, chalcones present the possibility to design advanced AED drugs. Further discovery of pharmacodynamics, safety profiles, and factors determining the efficiency of such chalcones will remain the key to enhancing the probability of chalcones becoming effective epilepsy treatments.