Molecular docking and molecular dynamic studies of semi-synthetic piperidine alkaloids as acetylcholinesterase inhibitors

Challenges in Designing Therapeutic Agents for Treating Alzheimer’s Disease-from Serendipity to Rationality

“…Danuello et al reported molecular modeling studies on two semi-synthetic acetyl derivatives of the piperidine alkaloids (-)cassine and (-)-spectaline isolated from S. spectabilis [295]. Danuello et al reported molecular modeling studies on two semi-synthetic acetyl derivatives of the piperidine alkaloids (-)cassine and (-)-spectaline isolated from S. spectabilis [295].…”

Mass spectrometry for characterization of homologous piperidine alkaloids and their activity as acetylcholinesterase inhibitors

“…Acetylcholinesterase (AChE) inhibition is the standard therapy for Alzheimer's disease (AD) – a late‐onset neurodegenerative pathology that impacts an individual's memory, motor coordination, and cognition in a progressive and eventually lethal manner . Alzheimer's disease has huge socio‐economic impact, and healthcare research in the twenty‐first century has prioritized the development of therapeutic alternatives to treat this condition …”

“…A mixture of the semi‐synthetic derivatives (−)‐3‐ O ‐acetylcassine ( 3 ) and (−)‐3‐ O ‐acetylspectaline ( 4 ) hydrochlorides, prepared from a mixture of the natural alkaloids (−)‐cassine ( 1 ) and (−)‐spectaline ( 2 ) (Figure ) isolated from S. spectabilis flowers, has been shown to inhibit AChE . This mixture presented both in vitro (IC 50 = 7.32 μM) and in vivo cholinergic activity during the spatial memory test (water maze) .…”

“…The obtained data indicated that the hydrochloride of molecule 3 is a better AChE inhibitor than the hydrochloride of molecule 4 possibly because the former molecule interacts with the target protein more favorably and at a lower desolvation cost. These results suggested that the side chain length considerably influences the inhibitory potential of the evaluated compounds …”

“…These results suggested that the side chain length considerably influences the inhibitory potential of the evaluated compounds. 9 To identify antimalarial prototypes, the piperidine alkaloids 1 and 2 isolated from S. spectabilis flowers and the semisynthetic derivatives 3 and 4 have been screened against a culture of Plasmodium falciparum-infected red blood cells. The natural compound 1, with shorter side chain, proved to be more effective against the parasite.…”