A novel series of multifunctional tacrine–quinoline hybrids were designed, synthesized, and evaluated as potential anti-Alzheimer’s agents. These compounds incorporate tacrine for cholinesterase’s inhibition and 8-hydroxyquinoline for metal chelation. Piperazine was selected as a linker to provide conformational flexibility and to create favorable cation–π interactions with residues in the mid-gorge region of AChE, enhancing dual-site binding with AChE to inhibit Aβ aggregation. In vitro studies demonstrated submicromolar inhibitory activity toward both AChE and BuChE, particularly for compounds 16e (IC₅₀ = 0.10 μM for AChE, 0.043 μM for BuChE) and 16h (IC₅₀ = 0.21 μM for AChE, 0.10 μM for BuChE). These compounds also exhibited potent inhibition of self-induced Aβ_1–42 aggregation (16e: 80.5% ± 4.4%, 16h: 93.2% ± 3.9% at 20 μM). Kinetic analyses revealed mixed-type inhibition, suggesting dual binding to both CAS and PAS of AChE. UV–vis spectrometry confirmed the chelation of Cu²⁺ and Zn²⁺ ions by the 8-hydroxyquinoline moiety. These findings highlight the tacrine–quinoline scaffold as a promising platform for the discovery of a multitarget-directed anti-AD drug.

A new series of tacrine–coumarin hybrids (compounds 15a–18b) linked by 1,2,3-triazole had been designed and synthesized as multifunctional ligands for the treatment of Alzheimer’s disease (AD). The inhibitory effects of the synthesized compounds on AChE and BuChE, their ability to inhibit Aβ aggregation, and their MAO inhibitory activities were evaluated. In vitro studies showed that some of the hybrids (compounds 17a–18b) exhibited significant abilities to inhibit both AChE and BuChE, self-induced Aβ aggregation, and MAO-B. In particular, compound 17d showed a well-balanced inhibitory profile against AChE and BuChE (IC₅₀ = 0.080 ± 0.007 μM for AChE, IC₅₀ = 0.044 ± 0.004 μM for BuChE), self-induced Aβ aggregation (58.4% ± 2.1% at 20 μM), and MAO-B (IC₅₀ = 0.18 ± 0.01 μM), suggesting that 17d might be an excellent multifunctional agent for AD treatment. In addition, compounds 15a and 15b were identified as selective inhibitors of BuChE at micromolar concentrations.

In recent years, the near-infrared (NIR) fluorescence theranostic system has garnered increasing attention for its advantages in the simultaneous diagnosis- and imaging-guided delivery of therapeutic drugs. However, challenges such as strong background fluorescence signals and rapid metabolism have hindered the achievement of sufficient contrast between tumors and surrounding tissues, limiting the system’s applicability. This study aims to integrate the pegylation strategy with a tumor microenvironment-responsive approach. A novel esterase-activated EPR strategy prodrug, OBHSA-PEG-DCM, was designed. This prodrug links OBHSA, a protein degrader capable of efficient ERα protein degradation, to the PEG-modified fluorescent group (dicyanomethylene-4H-pyran, DCM) via an ester bond. This integration facilitates targeted drug delivery and enhances the retention of the fluorescent group within the tumor, allowing distinct in vivo tumor imaging periods. Experimental results show that, benefiting from overexpressed esterase in cancer cells, OBHSA-PEG-DCM can be efficiently hydrolyzed, releasing OBHSA and pegylated DCM. OBHSA demonstrated potent inhibition against MCF-7 cells (IC₅₀ = 1.09 μM). Simultaneously, pegylated DCM exhibited remarkable in vivo imaging capabilities, lasting up to 12 days in mice, due to the enhanced permeability and retention (EPR) effect. OBHSA-PEG-DCM holds promise as a theranostic agent for ERα-positive breast cancer, offering both therapeutic and diagnostic capabilities. Importantly, this study highlights the utility of pegylated NIR fluorophores for long-circulating drug delivery systems, addressing current challenges in achieving high-contrast tumor imaging and effective targeted drug release.

Paeonia ostii is a commercially important ornamental and traditional medicinal plant esteemed in China. Salt stress is a widespread abiotic stress that significantly affects plant growth and development, and moderate stress can significantly promote the synthesis of plant secondary metabolites, requiring clarification of its underlying molecular mechanisms. The Salt Overly Sensitive 1 (SOS1) gene family is essential for salt stress tolerance, encoding Na⁺/H⁺ antiporters that preserve ion homeostasis and reduce cellular damage. This study conducted an extensive genome-wide analysis of the SOS1 gene family in Paeonia ostii, encompassing gene identification, characterization, three-dimensional and secondary structure prediction, gene structure and motif analysis, multiple alignments, phylogenetic tree construction, chromosomal localization, cis-regulatory element analysis, synteny analysis, Ka/Ks calculation, and gene expression analysis under salt stress treatments in three cultivars. Our findings identified 19 SOS1 genes within the P. ostii genome, demonstrating unique structural and functional attributes. All SOS1 genes were located on the plasma membrane and distributed across five chromosomes and two scaffolds. The conserved motif analysis results indicated that the SOS1 homologs had comparable protein structures. The coding sections of 19 PoSOS1 genes comprise amino acid sequences varying from 455 to 859, whereas the exons encompass amino acids ranging from 3 to 20. Furthermore, we discovered that the 2.5 kb upstream promoter region of the PoSOS1s gene has many cis-elements linked to phytohormones and stress responses. The phylogenetic study categorized the PoSOS1 genes into three subfamilies. In total, 38 miRNAs that target 19 PoSOS1 genes from 18 distinct families were identified. Conversely, gene expression analysis revealed six differentially expressed SOS1 genes in three distinct cultivars subjected to salt stress, with all six genes down-regulated and only one gene up-regulated in the QF-230 cultivar after six days of salt stress. This study offers new insights into the SOS1 gene family in P. ostii, elucidating its function in salt stress tolerance and establishing a foundation for future research on the functional characterization of SOS1 genes in P. ostii.