Profiling donepezil template into multipotent hybrids with antioxidant properties

Abstract

Alzheimer’s disease is debilitating neurodegenerative disorder in the elderly. Current therapy relies on administration of acetylcholinesterase inhibitors (AChEIs) -donepezil, rivastigmine, galantamine, and N-methyl-d-aspartate receptor antagonist memantine. However, their therapeutic effect is only short-term and stabilizes cognitive functions for up to 2 years. Given this drawback together with other pathological hallmarks of the disease taken into consideration, novel approaches have recently emerged to better cope with AD onset or its progression. One such strategy implies broadening the biological profile of AChEIs into so-called multi-target directed ligands (MTDLs). In this review article, we made comprehensive literature survey emphasising on donepezil template which was structurally converted into plethora of MTLDs preserving anti-cholinesterase effect and, at the same time, escalating the anti-oxidant potential, which was reported as a crucial role in the pathogenesis of the Alzheimer’s disease.

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“…One of the derivatives of 79 , for which X = H, R 1 = CF 2 H, R 2 = cyclopentylethyl, exhibited an IC 50 of 0.399 mM against PDE4D compared to rolipram as the reference compound (IC 50 0.621 mM), whereas the derivative showing X = H, R 1 = cyclopentylmethyl of family 84 exhibited the highest value among all tested compounds in the ORAC assay (its value is 1.98 expressed as Trolox equivalents). In this respect, the ORAC value of antioxidant activities increases the ability of a given compound as the antioxidant becomes better [ 58 ]. Clioquinol, rolipram, and roflumilast showed values of 0.60, 0.070, and 0.067, respectively.…”

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