Cardanol-derived AChE inhibitors: Towards the development of dual binding derivatives for Alzheimer's disease

Lemes, Laís Flávia Nunes; Ramos, Giselle de Andrade; Oliveira, Andressa Souza de; Silva, Fernanda Motta R. da; Couto, Gina C.; Boni, Marina da Silva; Guimarães, Marcos Jorge R.; Souza, Isis N. O.; Bartolini, Manuela; Andrisano, Vincenza; Nogueira, Patrícia Coelho do Nascimento; Silveira, Edilberto R.; Brand, Guilherme D.; Soukup, Ondřej; Korábečný, Jan; Romeiro, Nelilma C.; Castro, Newton G.; Bolognesi, María Laura; Romeiro, Luiz Antônio Soares

doi:10.1016/j.ejmech.2015.12.024

Cited by 81 publications

(61 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The ability of novel derivatives from 6-Cl-THA-scutellarin subset to permeate the BBB was predicted using a parallel artificial membrane permeation assay of the BBB (PAMPA-BBB) described by Di et al [ 58 , 59 ]. All the data are gathered in Table 4 .…”

Section: Resultsmentioning

confidence: 99%

Novel Tacrine-Scutellarin Hybrids as Multipotent Anti-Alzheimer’s Agents: Design, Synthesis and Biological Evaluation

et al. 2017

View full text Add to dashboard Cite

A novel series of 6-chlorotacrine-scutellarin hybrids was designed, synthesized and the biological activity as potential anti-Alzheimer’s agents was assessed. Their inhibitory activity towards human acetylcholinesterase (hAChE) and human butyrylcholinesterase (hBChE), antioxidant activity, ability to cross the blood-brain barrier (BBB) and hepatotoxic profile were evaluated in vitro. Among these compounds, hybrid K1383, bearing two methylene tether between two basic scaffolds, was found to be very potent hAChE inhibitor (IC50 = 1.63 nM). Unfortunately, none of the hybrids displayed any antioxidant activity (EC50 ≥ 500 μM). Preliminary data also suggests a comparable hepatotoxic profile with 6-Cl-THA (established on a HepG2 cell line). Kinetic studies performed on hAChE with the most active compound in the study, K1383, pointed out to a mixed, non-competitive enzyme inhibition. These findings were further corroborated by docking studies.

show abstract

Section: Resultsmentioning

confidence: 99%

Novel Tacrine-Scutellarin Hybrids as Multipotent Anti-Alzheimer’s Agents: Design, Synthesis and Biological Evaluation

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Anti-Alzheimer drugs are postulated to be centrally active, thus their effective permeation is necessary. To investigate the possibility of new huprine derivative (±)- 1 ·HCl to cross the blood-brain barrier (BBB), a parallel artificial membrane permeation assay (PAMPA) was used [ 50 , 51 ]. (±)-HupY is able to cross the BBB as suggested by previous ex vivo [ 39 , 49 ] and in vivo studies [ 26 ].…”

Section: Resultsmentioning

confidence: 99%

“…For the prediction of (±)- 1 ·HCl and (±)-HupY·HCl to passively penetrate the BBB, the PAMPA protocol was used [ 50 , 51 ]. Briefly, the filter membrane of the donor plate was coated with PBL (Polar Brain Lipid, Avanti, St. Normal, IL, USA) in dodecane (4 µL of 20 mg/mL PBL in dodecane) and the acceptor well was filled with 300 µL of PBS pH 7.4 buffer (VD).…”

Section: Methodsmentioning

confidence: 99%

Development of 2-Methoxyhuprine as Novel Lead for Alzheimer’s Disease Therapy

et al. 2017

View full text Add to dashboard Cite

Tacrine (THA), the first clinically effective acetylcholinesterase (AChE) inhibitor and the first approved drug for the treatment of Alzheimer’s disease (AD), was withdrawn from the market due to its side effects, particularly its hepatotoxicity. Nowadays, THA serves as a valuable scaffold for the design of novel agents potentially applicable for AD treatment. One such compound, namely 7-methoxytacrine (7-MEOTA), exhibits an intriguing profile, having suppressed hepatotoxicity and concomitantly retaining AChE inhibition properties. Another interesting class of AChE inhibitors represents Huprines, designed by merging two fragments of the known AChE inhibitors—THA and (−)-huperzine A. Several members of this compound family are more potent human AChE inhibitors than the parent compounds. The most promising are so-called huprines X and Y. Here, we report the design, synthesis, biological evaluation, and in silico studies of 2-methoxyhuprine that amalgamates structural features of 7-MEOTA and huprine Y in one molecule.

show abstract

“…Cardanol [66][67][68] Cardanol derivatives as new potential candidates of AChE inhibitors designed from nonisoprenoid phenolic lipids of cashew (NIPLs) of Anacardium occidentale nut-shell liquid have revealed favorable results. The development of cardanol derivatives seems to be attractive because of the abundance of the source of raw materials.…”

Section: Naturally Derived Cheismentioning

confidence: 99%

Alzheimer’s Disease Pharmacotherapy in Relation to Cholinergic System Involvement

et al. 2019

View full text Add to dashboard Cite

Alzheimer’s disease, a major and increasing global health challenge, is an irreversible, progressive form of dementia, associated with an ongoing decline of brain functioning. The etiology of this disease is not completely understood, and no safe and effective anti-Alzheimer’s disease drug to prevent, stop, or reverse its evolution is currently available. Current pharmacotherapy concentrated on drugs that aimed to improve the cerebral acetylcholine levels by facilitating cholinergic neurotransmission through inhibiting cholinesterase. These compounds, recognized as cholinesterase inhibitors, offer a viable target across key sign domains of Alzheimer’s disease, but have a modest influence on improving the progression of this condition. In this paper, we sought to highlight the current understanding of the cholinergic system involvement in Alzheimer’s disease progression in relation to the recent status of the available cholinesterase inhibitors as effective therapeutics.

show abstract

Cardanol-derived AChE inhibitors: Towards the development of dual binding derivatives for Alzheimer's disease

Cited by 81 publications

References 46 publications

Novel Tacrine-Scutellarin Hybrids as Multipotent Anti-Alzheimer’s Agents: Design, Synthesis and Biological Evaluation

Novel Tacrine-Scutellarin Hybrids as Multipotent Anti-Alzheimer’s Agents: Design, Synthesis and Biological Evaluation

Development of 2-Methoxyhuprine as Novel Lead for Alzheimer’s Disease Therapy

Alzheimer’s Disease Pharmacotherapy in Relation to Cholinergic System Involvement

Contact Info

Product

Resources

About