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[Display omitted] • Novel ferulic acid derivatives with oxadiazole were designed and synthesized. • The synthesized compounds showed significantly antiviral activity. • Compound 6 h can intensify the activities of some defensive enzymes. • 6 h regulates phenylpropanoid biosynthesis pathway and chloroplast function. • Some of the synthesized compounds could be used as potential elicitors. A series of new ferulic acid derivatives bearing an oxadiazole ether was synthesized by introducing a structure of oxadiazole into trans -ferulic acid via an ether linkage. The synthesized target compounds were evaluated in vivo for their anti-TMV (tobacco mosaic virus) activity, which indicated that some synthesized compounds displayed strong activity for controlling TMV. For protective activity, compounds 6f and 6 h had the most activities of 65% and 69.8% at 500 mg L-1, respectively. Compounds 6a , 6b , 6e , 6f and 6 h showed > 60% curative activities at 500 mg L-1. Preliminary proteomics analysis showed that compound 6 h could regulate the phenylpropanoid biosynthesis pathway and chloroplast function. These results indicated that synthesized novel ferulic acid derivatives could be used for controlling TMV. [ABSTRACT FROM AUTHOR]

• Compound 9d with memantine as a cap structure exhibits balanced anti-NMDAR and HDAC activity. • The structural activity relationship is explained in detail. • HDAC inhibitors of isohydroxamic showed a strong protective effect against hydrogen peroxide damage. Histone deacetylases (HDACs) have been indicated important roles in neurodegenerative disorders including Alzheimer's disease (AD). Herein, a series of novel compounds that contain a memantine moiety were designed to target HDACs and N -methyl- d -aspartate receptor (NMDAR) which are related to the treatment of AD. Biological characterization established that compound 9d exhibited a balanced inhibitory activity on NMDAR and HDACs. This compound is relatively selective to HDAC6 with IC 50 of 0.18 μM and also maintains comparable activity on NMDAR (K i = 0.59 μM) as memantine. Functionally, treatment with 9d increased the level of AcTubulin in MV4-11 cells and rescued PC-12 cells from H 2 O 2 -induced cytotoxicity with EC 50 of 0.94 μM. Studies in mice also demonstrated that compound 9d efficiently penetrates the blood brain barrier to reach the brain tissue. Collectively, the results strongly encourage further development of 9d as a potential therapeutic agent for AD. [ABSTRACT FROM AUTHOR]

• Twenty-eight derivatives were designed, synthesized, and biologically evaluated. • Some compounds were found to potently inhibit both AChE and HDAC. • Compounds exhibited potential Cu2+ chelating properties, and HDAC isoform inhibition selectivity. • Compound A10 could serve as apromising candidate analogs as AD therapeutics. In order to develop multitarget-directed ligands as potential treatments for Alzheimer's disease, twenty-eight new tacrine-hydroxamate derivatives were designed, synthesized, and biologically evaluated. As expected, most of the compounds exhibited inhibitory activities against cholinesterases (ChEs) and histone deacetylase (HDACs). Among the tested compounds, A10 showed not only potent and selective inhibition on AChE at sub-nanomolar potency (AChE IC50 = 0.12 nM, BChE IC50 = 361.52 nM) but also potent inhibition on HDAC (IC 50 = 0.23 nM). Moreover, A10 exhibited inhibitory activity on Aβ 1-42 self-aggregation as well as disaggregation activity on pre-formed Aβ fibrils. Furthermore, A10 exhibited antioxidant activity and metal chelating properties. Further mechanistic studies demonstrated that A10 is a pan-inhibitor of HDACs and a mixed-type inhibitor for AChE. It shown that A10 is a BBB penetrant by online prediction. Taken together, the results indicate that A10 can serve as a lead compound to develop promising candidate analogs as AD therapeutics. [ABSTRACT FROM AUTHOR]

[Display omitted] • Reynoutria multiflora (Thunb.) Moldenke suppresses prostate cancer growth in vitro and in vivo by inducing cell cycle arrest. • Reynoutria multiflora (Thunb.) Moldenke exhibits synergistic anti-tumor effects with AR antagonists in CRPC models. • Polygalacic acid derived from Reynoutria multiflora (Thunb.) Moldenke inhibits tumor growth by targeting CDC25B/CDK1 axis. Reynoutria multiflora (Thunb.) Moldenke (Polygonum multiflorum Thunb, PM) is a medicinal plant that was an element of traditional Chinese medicine (TCM) for centuries as a treatment for a wide range of conditions. Recent studies reported that PM suppressed prostate cancer growth in an AR-dependent manner. However, its role and mechanism in the treatment of advanced prostate cancer remain to be explored. This study aims to explore the anti-tumor role and potential mechanism of PM on prostate cancer. Cell viability, colony formation, fluorescence-activated cell sorting (FACS), and wound-healing assays were conducted to evaluate the tumor suppression effect of PM on lethal prostate cancer models in vitro. A xenograft mice model was established to detect the impact of PM on tumor growth and evaluate its biosafety in vivo. Integrative network pharmacology, RNA-seq, and bioinformatics were applied to determine the mechanisms of PM in prostate cancer. Molecular docking, cellular thermal shift assay (CETSA), CRISPR-Cas13, RT-qPCR, and WB were collaboratively employed to identify the potential anti-tumor ingredient derived from PM and its corresponding targets. PM significantly suppressed the growth of prostate cancer and sensitized prostate cancer to AR antagonists. Mechanistically, PM induced G2/M-phase cell-cycle arrest by modulating the phosphorylation of CDK1. Additionally, polygalacic acid derived from PM and its structural analog suppress prostate cancer growth by targeting CDC25B, a master regulator of the cell cycle that governs CDK1 phosphorylation. PM and its ingredient polygalacic acid suppress lethal prostate cancer growth by regulating the CDC25B-CDK1 axis to induce cell cycle arrest. [ABSTRACT FROM AUTHOR]