Thiratmatrakul_2014_Eur.J.Med.Chem_75C_21

Reference

Title : Synthesis, biological evaluation and molecular modeling study of novel tacrine-carbazole hybrids as potential multifunctional agents for the treatment of Alzheimer's disease - Thiratmatrakul_2014_Eur.J.Med.Chem_75C_21
Author(s) : Thiratmatrakul S , Yenjai C , Waiwut P , Vajragupta O , Reubroycharoen P , Tohda M , Boonyarat C
Ref : Eur Journal of Medicinal Chemistry , 75C :21 , 2014
Abstract :

New tacrine-carbazole hybrids were developed as potential multifunctional anti-Alzheimer agents for their cholinesterase inhibitory and radical scavenging activities. The developed compounds showed high inhibitory activity on acetylcholinesterase (AChE) with IC50 values ranging from 0.48 to 1.03 muM and exhibited good inhibition selectivity against AChE over butyrylcholinesterase (BCHE). Molecular modeling studies revealed that these tacrine-carbazole hybrids interacted simultaneously with the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. The derivatives containing methoxy group showed potent ABTS radical scavenging activity. Considering their neuroprotection, our results indicate that these derivatives can reduce neuronal death induced by oxidative stress and beta-amyloid (Abeta). Moreover, S1, the highest potency for both radical scavenging and AChE inhibitory activity, exhibited an ability to improve both short-term and long-term memory deficit in mice induced by scopolamine. Overall, tacrine-carbazole derivatives can be considered as a candidate with potential impact for further pharmacological development in Alzheimer's therapy.

PubMedSearch : Thiratmatrakul_2014_Eur.J.Med.Chem_75C_21
PubMedID: 24508831

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Citations formats

Thiratmatrakul S, Yenjai C, Waiwut P, Vajragupta O, Reubroycharoen P, Tohda M, Boonyarat C (2014)
Synthesis, biological evaluation and molecular modeling study of novel tacrine-carbazole hybrids as potential multifunctional agents for the treatment of Alzheimer's disease
Eur Journal of Medicinal Chemistry 75C :21

Thiratmatrakul S, Yenjai C, Waiwut P, Vajragupta O, Reubroycharoen P, Tohda M, Boonyarat C (2014)
Eur Journal of Medicinal Chemistry 75C :21