Multi-Target Actions of Acridones from Atalantia monophylla towards Alzheimer’s Pathogenesis and Their Pharmacokinetic Properties

Abstract

Ten acridones isolated from Atalantia monophylla were evaluated for effects on Alzheimer’s disease pathogenesis including antioxidant effects, acetylcholinesterase (AChE) inhibition, prevention of beta-amyloid (Aβ) aggregation and neuroprotection. To understand the mechanism, the type of AChE inhibition was investigated in vitro and binding interactions between acridones and AChE or Aβ were explored in silico. Drug-likeness and ADMET parameters were predicted in silico using SwissADME and pKCSM programs, respectively. All acridones showed favorable drug-likeness and possessed multifunctional activities targeting AChE function, Aβ aggregation and oxidation. All acridones inhibited AChE in a mixed-type manner and bound AChE at both catalytic anionic and peripheral anionic sites. In silico analysis showed that acridones interfered with Aβ aggregation by interacting at the central hydrophobic core, C-terminal hydrophobic region, and the key residues 41 and 42. Citrusinine II showed potent multifunctional action with the best ADMET profile and could alleviate neuronal cell damage induced by hydrogen peroxide and Aβ1-42 toxicity.

Four New Anthraquinones with Histone Deacetylase Inhibitory Activity from Ventilago denticulata Roots

“…Drug-likeness is a useful concept in drug design that increases the chances of chemical entities and avoids drug development failure. In this study, the SwissADME web server ( , accessed on 30 December 2021) was performed to estimate the physicochemical features of anthraquinones 1 – 4 , to assess their drug-likeness [ 21 ]. The results ( Table 4 ) showed that 1 – 4 presented no violation of Lipinski’s rules.…”

Reduction of Acetylcholinesterase Inhibition Activity of Antiscolic Herbal Compounds by Bacilli Probiotics

“…Trp84, Phe330 and His440 were identical binding sites for both substrate (acetylcholine) and inhibitor (matrine, berberine or osthole). In previous papers, amino acids Trp84, Tyr130, Phe330 and Phe331 are responsible for the molecular recognition of quaternary ammonium ligands and also the catalytic anionic sites (Lee et al 2015;Takomthong et al 2021). Therefore, the three AHCs probably inhibit AchE through competitively occupation of the active catalytic channel.…”

HPLC-MS Profiling, Antioxidant, Antimicrobial, Antidiabetic, and Cytotoxicity Activities of Arthrocnemum indicum (Willd.) Moq. Extracts

“…In addition, they can promote several biological activities implicated in preventing cancer, chronic inflammation, cardiovascular disorders, and neurodegenerative disease [11][12][13][14]. Oxidative stress has been implicated in Alzheimer's disease (AD); memory impairment in AD patients is related to the decline in the acetylcholine (ACh) level in the cholinergic system [15]. Therefore, AChE inhibitors are used for stabilizing the ACh neurotransmitter levels in the synaptic cleft [15].…”

“…Oxidative stress has been implicated in Alzheimer's disease (AD); memory impairment in AD patients is related to the decline in the acetylcholine (ACh) level in the cholinergic system [15]. Therefore, AChE inhibitors are used for stabilizing the ACh neurotransmitter levels in the synaptic cleft [15]. On the other hand, a large number of halophyte plants have been traditionally used to reduce blood pressure (Salsola kali L., Chenopodiaceae), for the treatment of cancer (Artemisia scopariae Waldst.…”