Neuroprotective activities of coumarin-chalcone derivatives: A comprehensive mechanistic review

Coumarin-chalcone hybrids have recently evolved as lead multitarget-directed ligands for the development of neurodegenerative disorders such as Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis. Their flexibility offers a unique advantage of targeting multiple key pathological events like the inhibition of MAO-B and AChE, scavenging of ROS, hindrance of neuroinflammatory mediators through the inhibition of the NLRP۱/ NLRP۳ inflammasome, and inhibition of Aβ/tau protein fibril formation. Even a considerable number of findings from in vitro screenings for the neuroprotective role of lead hybrids such as LM۰۲۱, LM۰۳۶, and ChC۴ showed unique advantages of these hybrids, from activating CREB to preferential inhibition of enzymes. Even now, considerable hurdles lie along the lines of transferring lab findings to practical applications, especially because of the lack of validation of properties for in vitro-cultivated hybrids. Future perspectives include optimization of structure, ADMET-assisted hybrid design, and testing of hybrids on animals to improve a series of parameters such as bioavailability, blood-brain barrier penetration, and toxicity. Overall, coumarin-chalcone hybrids can be termed a novel set of molecules possessing immense capability to combat the multidrug-resistant property of neurodegenerative disorders.

کلیدواژه ها:

Coumarin-chalcone hybrids ، Enzyme inhibition ، Inflammatory Effects ، neuroinflammation ، Blood-brain barrier permeability