Design, Synthesis, and Biological Evaluation of a New Series of Biphenyl/Bibenzyl Derivatives Functioning as Dual Inhibitors of Acetylcholinesterase and Butyrylcholinesterase

Wang, Dongmei; Feng, Bo; Fu, Hui Zheng; Liu, Ailin; Wang, Lin; Du, Guanhua; Wu, Song

doi:10.3390/molecules22010172

Cited by 14 publications

(4 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our previous study, a series of symmetrical molecules containing biphenyl/bibenzyl scaffolds were designed, synthesized, and evaluated for inhibitory activities towards both AChE and BuChE [ 17 ]. Among them, DL0410 showed the strongest AChE and BuChE inhibitory activities.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Novel Dual Acetyl- and Butyrylcholinesterase Inhibitors as Potential Anti-Alzheimer’s Disease Agents Using Pharmacophore, 3D-QSAR, and Molecular Docking Approaches

Pang

Fu²,

Yang

et al. 2017

Molecules

Self Cite

View full text Add to dashboard Cite

DL0410, containing biphenyl and piperidine skeletons, was identified as an acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitor through high-throughput screening assays, and further studies affirmed its efficacy and safety for Alzheimer’s disease treatment. In our study, a series of novel DL0410 derivatives were evaluated for inhibitory activities towards AChE and BuChE. Among these derivatives, compounds 6-1 and 7-6 showed stronger AChE and BuChE inhibitory activities than DL0410. Then, pharmacophore modeling and three-dimensional quantitative structure activity relationship (3D-QSAR) models were performed. The R2 of AChE and BuChE 3D-QSAR models for training set were found to be 0.925 and 0.883, while that of the test set were 0.850 and 0.881, respectively. Next, molecular docking methods were utilized to explore the putative binding modes. Compounds 6-1 and 7-6 could interact with the amino acid residues in the catalytic anionic site (CAS) and peripheral anionic site (PAS) of AChE/BuChE, which was similar with DL0410. Kinetics studies also suggested that the three compounds were all mixed-types of inhibitors. In addition, compound 6-1 showed better absorption and blood brain barrier permeability. These studies provide better insight into the inhibitory behaviors of DL0410 derivatives, which is beneficial for rational design of AChE and BuChE inhibitors in the future.

show abstract

Section: Introductionmentioning

confidence: 99%

Evaluation of Novel Dual Acetyl- and Butyrylcholinesterase Inhibitors as Potential Anti-Alzheimer’s Disease Agents Using Pharmacophore, 3D-QSAR, and Molecular Docking Approaches

Pang

Fu²,

Yang

et al. 2017

Molecules

Self Cite

View full text Add to dashboard Cite

show abstract

“…After being buried in the hydrophobic pocket, lipophilic moieties interact with the non-polar residues and displace water molecules, enhancing the affinity of the inhibitors to the target receptor. On the other hand, biphenyls are characterized by strong hydrophobicity, good lipid solubility, cell membrane permeability, and metabolic stability [ 21 , 22 ] and are important molecular skeletons in many agrochemicals ( Figure 1 A) [ 23 ]. Also, biphenyls can be easily synthesized via transition-metal-catalyzed Suzuki–Miyaura cross-coupling reaction, one of the most powerful tools for the construction of the biphenyl core [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

Discovery of a New Class of Lipophilic Pyrimidine-Biphenyl Herbicides Using an Integrated Experimental-Computational Approach

Yan,

Chen,

et al. 2024

Molecules

View full text Add to dashboard Cite

Herbicides are useful tools for managing weeds and promoting food production and sustainable agriculture. In this study, we report on the development of a novel class of lipophilic pyrimidine-biphenyl (PMB) herbicides. Firstly, three PMBs, Ia, IIa, and IIIa, were rationally designed via a scaffold hopping strategy and were determined to inhibit acetohydroxyacid synthase (AHAS). Computational simulation was carried out to investigate the molecular basis for the efficiency of PMBs against AHAS. With a rational binding mode, and the highest in vitro as well as in vivo potency, Ia was identified as a preferable hit. Furthermore, these integrated analyses guided the design of eighteen new PMBs, which were synthesized via a one-step Suzuki–Miyaura cross-coupling reaction. These new PMBs, Iba-ic, were more effective in post-emergence control of grass weeds compared with Ia. Interestingly, six of the PMBs displayed 98–100% inhibition in the control of grass weeds at 750 g ai/ha. Remarkably, Ica exhibited ≥ 80% control against grass weeds at 187.5 g ai/ha. Overall, our comprehensive and systematic investigation revealed that a structurally distinct class of lipophilic PMB herbicides, which pair excellent herbicidal activities with new interactions with AHAS, represent a noteworthy development in the pursuit of sustainable weed control solutions.

show abstract

“…The biphenyl is normally used as an advantaged and functional moiety in the field of drug design and the process of medicinal advancement ( Lu et al, 2015 ; Anusha et al, 2016 ; Tarade et al, 2017 ; Delgado et al, 2019 ). They have the potentials to be developed as prospecting therapeutic agents for a range of diseases ( Chen et al, 2022 ), such as the dual inhibitors of acetylcholinesterase and butyrylcholinesterase ( Wang et al, 2017 ) for Alzheimer’s disease ( Inuzuka et al, 2022 ), the transient receptor potential vanilloid type 1 (TRPV1) antagonist ( Oka et al, 2018 ), the human immunodeficiency virus -1 (HIV-1) nonnucleoside reverse transcriptase inhibitor ( Sang et al, 2019 ). In addition, they could also be applied as auxiliary parts to enhance the biological properties ( Ding et al, 2015 ) or act as chiroptical probes ( Santoro et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Biphenyls in Clusiaceae: Isolation, structure diversity, synthesis and bioactivity

et al. 2022

View full text Add to dashboard Cite

Clusiaceae plants contain a wide range of biologically active metabolites that have gotten a lot of interest in recent decades. The chemical compositions of these plants have been demonstrated to have positive effects on a variety of ailments. The species has been studied for over 70 years, and many bioactive compounds with antioxidant, anti-proliferative, and anti-inflammatory properties have been identified, including xanthones, polycyclic polyprenylated acylphloroglucinols (PPAPs), benzophenones, and biphenyls. Prenylated side chains have been discovered in many of these bioactive substances. To date, there have been numerous studies on PPAPs and xanthones, while no comprehensive review article on biphenyls from Clusiaceae has been published. The unique chemical architectures and growing biological importance of biphenyl compounds have triggered a flurry of research and interest in their isolation, biological evaluation, and mechanistic studies. In particular, the FDA-approved drugs such as sonidegib, tazemetostat, daclatasvir, sacubitril and trifarotene are closely related to their biphenyl-containing moiety. In this review, we summarize the progress and development in the chemistry and biological activity of biphenyls in Clusiaceae, providing an in-depth discussion of their structural diversity and medicinal potential. We also present a preliminary discussion of the biological effects with or without prenyl groups on the biphenyls.

show abstract

Design, Synthesis, and Biological Evaluation of a New Series of Biphenyl/Bibenzyl Derivatives Functioning as Dual Inhibitors of Acetylcholinesterase and Butyrylcholinesterase

Cited by 14 publications

References 17 publications

Evaluation of Novel Dual Acetyl- and Butyrylcholinesterase Inhibitors as Potential Anti-Alzheimer’s Disease Agents Using Pharmacophore, 3D-QSAR, and Molecular Docking Approaches

Evaluation of Novel Dual Acetyl- and Butyrylcholinesterase Inhibitors as Potential Anti-Alzheimer’s Disease Agents Using Pharmacophore, 3D-QSAR, and Molecular Docking Approaches

Discovery of a New Class of Lipophilic Pyrimidine-Biphenyl Herbicides Using an Integrated Experimental-Computational Approach

Biphenyls in Clusiaceae: Isolation, structure diversity, synthesis and bioactivity

Contact Info

Product

Resources

About