Design, synthesis and evaluation of pterostilbene β-amino alcohol derivatives as multifunctional agents for Alzheimer's disease treatment

Zheng, Yunxiaozhu; Qiang, Xiaoming; Xu, Rui; Song, Qing; Tian, Chaoquan; Liu, Hongyan; Li, Wei; Tan, Zhenghuai; Deng, Yong

doi:10.1016/j.bioorg.2018.03.016

Cited by 20 publications

(8 citation statements)

References 41 publications

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“…Therefore, pterostilbene can be used in the design and development of new drugs for the treatment and prevention of related diseases, and its broad application prospects are of great interest to researchers [ 21 , 22 ]. Zheng et al designed and synthesized a series of pterostilbene derivatives, of which compound 5f ( Figure 1 A) exhibited high anti-oxidative activity and neuroprotective effects [ 23 ]. Chen et al designed and synthesized 37 new resveratrol flavanol derivatives, of which compound 7f ( Figure 1 A) could inhibit the transduction of NF-κB cell signaling pathway caused by TLR4 activation and attenuate lipopolysaccharide-induced acute lung injury (ALI) in mice [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Discovery of Novel Pterostilbene Derivatives That Might Treat Sepsis by Attenuating Oxidative Stress and Inflammation through Modulation of MAPKs/NF-κB Signaling Pathways

et al. 2021

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Sepsis remains one of the most common life-threatening illnesses that is characterized by a systemic inflammatory response syndrome (SIRS) and usually arises following severe trauma and various septic infections. It is still in urgent need of new effective therapeutic agents, and chances are great that some candidates can be identified that can attenuate oxidative stress and inflammatory responses. Pterostilbene, which exerts attractive anti-oxidative and anti-inflammatory activities, is a homologue of natural polyphenolic derivative of resveratrol. Starting from it, we have made several rounds of rational optimizations. Firstly, based on the strategy of pharmacophore combination, indanone moiety was introduced onto the pterostilbene skeleton to generate a novel series of pterostilbene derivatives (PIF_1–PIF_16) which could possess both anti-oxidative and anti-inflammatory activities for sepsis treatment. Then, all target compounds were subjected to their structure–activity relationships (SAR) screening of anti-inflammatory activity in mouse mononuclear macrophage RAW264.7 cell line, and their cytotoxicities were determined after. Finally, an optimal compound, PIF_9, was identified. It decreased the mRNA levels of lipopolysaccharide (LPS)-induced interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), and cyclooxygenase 2 (COX2). We also found that the anti-inflammatory effects might be contributed by its suppression on the nuclear factor-κB (NF-κB) and MAPKs signaling pathway. Moreover, PIF_9 also demonstrated potent anti-oxidative activity in RAW264.7 macrophages and the sepsis mouse model. Not surprisingly, with the benefits mentioned above, it ameliorated LPS-induced sepsis in C57BL/6J mice and reduced multi-organ toxicity. Taken together, PIF_9 was identified as a potential sepsis solution, targeting inflammation and oxidative stress through modulating MAPKs/NF-κB.

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Section: Introductionmentioning

confidence: 99%

Discovery of Novel Pterostilbene Derivatives That Might Treat Sepsis by Attenuating Oxidative Stress and Inflammation through Modulation of MAPKs/NF-κB Signaling Pathways

et al. 2021

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“…Compounds D1–D24 can be easily obtained by reported methods [ 34 , 38 ]. The synthetic route for preparation of the target compounds is depicted in Scheme 1 .…”

Section: Methodsmentioning

confidence: 99%

“…A large part of the literature on asymmetric amino hydroxylation focuses on its application in the synthesis of bioactive compounds, many β -amino alcohol derivatives have widely been concerned for their good biological activity [ 29 , 30 ]. Including antiviral [ 31 ], antibacterial [ 32 , 33 ], antioxidative [ 34 ], anti-inflammatory [ 35 ], anti-proliferative [ 36 ], and anti-cancer [ 37 ] properties. Some of the active compounds containing β -amino alcohol scaffold are exemplified in Fig.…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis, and bioactivity of ferulic acid derivatives containing an β-amino alcohol

Dai

Huang

et al. 2022

BMC Chemistry

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Background Plant diseases caused by viruses and bacteria cause huge economic losses due to the lack of effective control agents. New potential pesticides can be discovered through biomimetic synthesis and structural modification of natural products. A series of ferulic acid derivatives containing an β-amino alcohol were designed and synthesized, and their biological activities were evaluated. Result Bioassays results showed that the EC50 values of compound D24 against Xanthomonas oryzae pv. oryzae (Xoo) was 14.5 μg/mL, which was better than that of bismerthiazol (BT, EC50 = 16.2 μg/mL) and thiodiazole copper (TC, EC50 = 44.5 μg/mL). The in vivo curative and protective activities of compound D24 against Xoo were 50.5% and 50.1%, respectively. The inactivation activities of compounds D2, D3 and D4 against tobacco mosaic virus (TMV) at 500 μg/mL were 89.1, 93.7 and 89.5%, respectively, superior to ningnanmycin (93.2%) and ribavirin (73.5%). In particular, the EC50 value of compound D3 was 38.1 μg/mL, and its molecular docking results showed that compound D3 had a strong affinity for TMV-CP with a binding energy of − 7.54 kcal/mol, which was superior to that of ningnanmycin (− 6.88 kcal /mol). Conclusions The preliminary mechanism research results indicated that compound D3 may disrupt the three-dimensional structure of the TMV coat protein, making TMV particles unable to self-assemble, which may provide potential lead compounds for the discovery of novel plant antiviral agents. Graphical Abstract

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“…It has been reported that the tertiary amine unit was an essential cholinesterase inhibitor pharmacophore, which can promote the hydrogen bond interaction between the compound backbone and the AChE catalytic site, thereby inhibiting AChE activity . Therefore, Zheng et al (2018) reported that a key fragment of pterostilbene was hybridized with a tertiary amine unit using a carbon chain containing a chiral hydroxyl group to design a rosandalene β-aminoalcohol derivative (compounds 4-17) with anti-AD potential. In order to synthesize the desired target compounds 4-17, they chose Scheme 1, starting with pterostilbene and completing the reaction in two steps.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and activities of acetylcholinesterase inhibitors

Zhou

Huang

2021

Chem Biol Drug Des

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Cholinesterase (ChE) inhibitors can be divided into two categories: acetylcholinesterase (AChE) inhibitors and butylcholinesterase (BuChE) inhibitors.Therefore, the development of selective inhibition of AChE and BuChE activities is the central content of ChE pharmacochemistry research. In order to clarify the progress of AChE inhibitor-based design, synthesis, and activity studies, we reviewed the pharmacochemical and pharmacological properties of selective AChE inhibitors over the past decade. We hope that this review will make it easier for readers to understand the development of new drug chemistry methods for AChE inhibitors in order to develop more effective and selective AChE inhibitors.

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Design, synthesis and evaluation of pterostilbene β-amino alcohol derivatives as multifunctional agents for Alzheimer's disease treatment

Cited by 20 publications

References 41 publications

Discovery of Novel Pterostilbene Derivatives That Might Treat Sepsis by Attenuating Oxidative Stress and Inflammation through Modulation of MAPKs/NF-κB Signaling Pathways

Discovery of Novel Pterostilbene Derivatives That Might Treat Sepsis by Attenuating Oxidative Stress and Inflammation through Modulation of MAPKs/NF-κB Signaling Pathways

Design, synthesis, and bioactivity of ferulic acid derivatives containing an β-amino alcohol

Synthesis and activities of acetylcholinesterase inhibitors

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