Synthesis, biological evaluation and molecular modeling study of novel tacrine–carbazole hybrids as potential multifunctional agents for the treatment of Alzheimer's disease

Thiratmatrakul, Supatra; Yenjai, Chavi; Waiwut, Pornthip; Vajragupta, Opa; Reubroycharoen, Prasert; Tohda, Michihisa; Boonyarat, Chantana

doi:10.1016/j.ejmech.2014.01.020

Cited by 137 publications

(85 citation statements)

References 34 publications

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“…Several crystallographic studies and original computational analysis have demonstrated that the tricycle ring have interacted strong parallel π-π stacking against the indole ring of Trp84 [14,[34][35][36]. Hydrophobic contacts have also been observed between the ring system and Ser200, His440 and Phe331.…”

Section: Inhibition Mechanism Of Achementioning

confidence: 92%

Synthesis, antioxidant and anticholinesterase activities of novel coumarylthiazole derivatives

Kurt

Gazioğlu

Sönmez

et al. 2015

Bioorganic Chemistry

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Section: Inhibition Mechanism Of Achementioning

confidence: 92%

Synthesis, antioxidant and anticholinesterase activities of novel coumarylthiazole derivatives

Kurt

Gazioğlu

Sönmez

et al. 2015

Bioorganic Chemistry

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“…Accordingly, the development of tacrine-based dimers and hybrids with improved pharmacological properties as well as mitigated side effects has been the hub of attention in recent years (8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

Molecular Docking and PLIF Studies of Novel Tacrine-Naphtoquinone Hybrids Based on Multi-Target-Directed Ligand Approach for Alzheimer’s Disease

Fereidoonnezhad

Mostoufi

Zali

et al. 2017

Jundishapur J Nat Pharm Prod

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Alzheimer's disease (AD), the most typical type of dementia and memory loss, is a complicated and progressive neurodegenerative disorder. Due to the multi-factorial etiology of AD, the multi-target-directed ligand (MTDL) approach can be a potential method in seeking new drug candidates for this disease. In this study, over 200 tacrine-naphtoquinone hybrids have been designed and their drug-likeness, molecular docking, and descriptor analysis were conducted to find out a drug candidate with less toxicity and better binding affinity than tacrine. The Docking analysis was conducted using human acetylcholineesterase (1ACJ), human butyrylcholineesterase (4BDS), and β-secretase (BACE1) (1w51) enzymes using Autodock 4.2 and Vina. Promising results were obtained on the types of interactions. Based on molecular docking on 3 targets as well as protein ligand interaction fingerprint (PLIF) studies, the compounds with better results were introduced as good candidates for synthesis. The validity of docking protocols was confirmed using a set of familiar active ligands and decoys on these targets by means of 2 known statistical metrics such as the receiver-operating characteristic (ROC) and Enrichment Factor (EF). Structure activity relationship (SAR) studies, in these class of compounds, show that the hydroxyethylamine, as a linker, is an essential group to improving binding site to AChE and BACE-1 targets.

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“…Numerous reports indicate that trolox can protect liver from the damage induced by chemical insults both in vitro and in vivo [26e28]. In addition, it showed neuroprotective effect through scavenging ROS and attenuating the neurotoxicity mediated by Ab and H 2 O 2 on hippocampal neurons [29,30]. Furthermore, as a lipidsoluble analog of trolox, Vitamin E has been already used to prevent the tacrine-induced hepatotoxicity in clinic and delay the AD progression in patients with moderately severe AD [18,31].…”

Section: Introductionmentioning

confidence: 98%

Multifunctional tacrine–trolox hybrids for the treatment of Alzheimer's disease with cholinergic, antioxidant, neuroprotective and hepatoprotective properties

Xie

Lan

Wang

et al. 2015

European Journal of Medicinal Chemistry

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Synthesis, biological evaluation and molecular modeling study of novel tacrine–carbazole hybrids as potential multifunctional agents for the treatment of Alzheimer's disease

Cited by 137 publications

References 34 publications

Synthesis, antioxidant and anticholinesterase activities of novel coumarylthiazole derivatives

Synthesis, antioxidant and anticholinesterase activities of novel coumarylthiazole derivatives

Molecular Docking and PLIF Studies of Novel Tacrine-Naphtoquinone Hybrids Based on Multi-Target-Directed Ligand Approach for Alzheimer’s Disease

Multifunctional tacrine–trolox hybrids for the treatment of Alzheimer's disease with cholinergic, antioxidant, neuroprotective and hepatoprotective properties

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