CURRENT ORGANIC SYNTHESIS
·
2021
·Vol. 18
·期 6
·587-591
·
IF 1.975
Song Zurong,Lu Qin,Tao Ali,Wu Tianchen
Background: Paclitaxel, a natural diterpenoid compound, has anti-tumor effect by acting on tubulin, whereas coumarin, another kind of natural product, has anti-tumor effect, along with some other effects, such as anti-bacterial-., Moreover, it also possesses fluorescence. Objective:
Multi targeting is an effective strategy in drug design to combat tumor. Therefore, a combination of paclitaxel with other active molecular drugs for exploring the novel lead with multi-functions is in demand. Materials and Methods: To synthsize paclitaxel-coumarin conjugate via click
chemistry and to investigate anticancer activity by MTT assay and the scratch test. Results and Discussion: The results of MTT assay showed that compared tothe paclitaxel, the anti-tumor activity of the conjugate was significantly improved. The results of flow cytometry showed that the
conjugate had a stronger ability to induce apoptosis. The scratch test results showed that the conjugate had better anti- metastasis ability than paclitaxel. Conclusion: These findings indicated that paclitaxel and coumarin had a synergistic effect, which paved the way for the development
of paclitaxel through fluorescence.
研究领域:
药理学
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肿瘤学
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药物化学
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2025
·
IF 6.5
Zi-Yun Wu,Kang-Yu Qiu,Yan-Jun Gai,Jia-Hui Wu,Bo-Xuan Zhou,Qing-Feng Shi
Breast cancer is one of the most common cancers among women worldwide, exhibiting notably high incidence and mortality rates. Despite its high fatality, a comprehensive study that mechanism and treatment of herbal medicines has not yet been conducted. Quercetin, a natural flavonoid, exhibits multi-targeted therapeutic potential against breast cancer. The aim of this study is to investigate and assess the mechanism and treatment of quercetin in breast cancer. We collected articles published within five years using PubMed, Google Scholar, and Web of Science with “breast cancer” and “quercetin” as
研究领域:
肿瘤学
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药理学
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天然产物
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Xian Liu,Qiwu Yuan,Yang Yang,Ke Li,Nanjiong Pang,Jiangtao Wang,Ming Yang,Xia Li,Junling Guo,Xuepin Liao,Bi Shi
Antibiotic resistance poses a significant threat to global public health, urgently demanding the development of new antibacterial agents with high efficacy and low resistance potential. In this study, we engineered self-assembled nanocomplexes of the gallic acid (GA) with rare earth (Re) ions (Ce 3+ , Gd 3+ , and Yb 3+ ), leveraging the unique multidentate structures of polyphenols to enhance antibacterial performance while minimizing resistance. These GA-Re nanocomplexes demonstrated potent activity against both antibiotic-sensitive Staphylococcus aureus (ASSA) and methicillin-resistant S. aureus (MRSA), with minimum inhibitory concentrations as low as 0.5 mmol/L. Viable MRSA cell numbers decreased from 7.40 × 10 7 CFU/mL to 8.43 × 10 6 and 7.33 × 10 2 CFU/mL when treated with penicillin (PEN) and GA-Gd for 24 h, respectively, indicating higher bactericidal efficiency of GA-Gd. Remarkably, no resistance developed in ASSA even after 60 days(d) of continuous exposure to GA-Gd, in contrast to the significant resistance observed with PEN (1024-fold) and neomycin (256-fold) after 28 d. The multidentate structure of GA facilitated versatile interactions with bacterial surface structures, enabling multiple mechanisms of action targeting cell walls, membranes, DNA, and cellular metabolism. Moreover, in vivo studies revealed that GA-Gd was effectively metabolized and excreted without accumulation or toxicity, and also accelerates the healing of MRSA infected wounds. These findings suggest the potential of self-assembled Re-based phenolic nanocomplexes as promising candidates for combating antibiotic-resistant bacterial infections, and pave the way for next-generation antibacterial agents.
研究领域:
微生物学
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药理学
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材料科学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
He Zhang,Jun Tang,Huiliang Cao,Chenguang Wang,Chong Shen,Jun Liu
Ethnopharmacological relevance Colorectal cancer (CRC) is a prevalent malignant tumor of the digestive tract. Traditional Chinese medicine (TCM) has a long history of treating CRC, with advantages such as effectiveness, multi-target, multi-pathway, and minimal side effects. TCM Magnolia officinalis (M. officinalis) refers to the dried bark, root bark, and branch bark of either Magnolia officinalis Rehd.et Wils. or Magnolia officinalis Rehd.et Wils. var. biloba Rehd.et Wils . It is commonly utilized to alleviate the side effects of chemotherapy for CRC, owing to its anti-inflammatory and anti-tumor properties. However, current research primarily focuses on the individual components and does not take into consideration the characteristics of multi-component-multi-target action. Aim of the study Our aim is to study the new action characteristics of M. officinalis in the treatment of CRC. Materials and methods Utilizing network pharmacology to identify potential active ingredients, key targets, and main signaling pathways of M. officinalis for the treatment of CRC. The binding effect was further validated through molecular docking analysis. Furthermore, the aforementioned components were identified using liquid chromatography-mass spectrometry (LC-MS), and the cleavage pathways of the main components were analyzed. Subsequently, both in vitro and in vivo experiments were carried out to investigate the anti-CRC effect of the active ingredients of M. officinalis and its potential mechanism. Results Network pharmacology and Molecular docking identified 5 main active ingredients and 6 core targets of M. officinalis for the treatment of CRC. Then, LC-MS identified the active components of M. officinalis. At the same time, both in vitro and in vivo experiments have confirmed the ability of Eucalyptol (Euc) and Obovatol (Obo)to inhibit inflammation and tumor cell proliferation. The possible mechanism involved is that Euc and Obo counteract CRC by inhibiting the over-activation of NF-κBp65/JAK and Bcl-2/Caspase signaling pathways, respectively. They also play a role in the anti-CRC effect of M. officinalis. Conclusion Magnolol (MAG), Honokiol (HK), Euc, Obo, and Neohesperidin (NHP) in M. officinalis may be the pharmacological substance basis for its anti-cancer effect on CRC. The treatment of CRC with M. officinalis is characterized by its multi-component, multi-target, and multi-pathway approach. These findings provide a theoretical basis for further inspiring the clinical application of M. officinalis and the development of efficacy targets.
研究领域:
民族药理学
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肿瘤学
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药理学
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中药学
✓ 已验证
DOI
PubMed
高影响因子
ANALYTICAL LETTERS
·
2022
·
IF 2.267
Ru Li,Xuan Zou,Pan Luan,Xiaokun Liu,Ning Wang,Qian Wang,Huashi Guan,Zhe Xu
Thrombosis is the main cause of many cardiovascular diseases. The conventional pharmaceuticals used for preventing thrombosis can induce significant adverse side effects, especially bleeding risk. Hence, the development of more effective and safe antithrombotic agents is strongly demanded to improve clinical treatment. In order to rapidly screen and identify novel antithrombotic substances from natural marine products, a multi-target screening strategy is reported to quantify the antithrombotic activity with high-performance liquid chromatography – mass spectrometry (HPLC-MS). Five key thrombosis-related targets, including thrombin, coagulation factors Xa, XIa and XIIa and platelet phosphodiesterase 3, were selected to establish the multi-target antithrombotic activity screening assay. The Michaelis-Menten constants (Km) were 8.16 µM, 58.85 µM, 120.03 µM, 35.24 µM and 79.67 µM, respectively. Five known inhibitors, namely argatroban, rivaroxaban, benzamidine, 3-carboxamide-coumarinand, and milrinone, were used for validation. The reproducibility of the screening strategy was verified by calculating the overall average Z′ value, which was 0.88. Subsequently, this method was assessed by screening a small marine library of 78 compounds. Five coumarin compounds were selected, and their antithrombotic activities were further validated in standard assessments of enzyme inhibition and on the coagulometer. According to the validation, the multi-target assay based on dried blood spots and HPLC-MS was suitable for screening antithrombotic substances with considerable reliability.
研究领域:
药理学
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分析化学
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心血管病学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2024
·
IF 6.8
Yuanjiang Wang,Jianluo Zhang,Kun Li,Shengjin Xia,Shaohua Gou
In this work, a series of multitargeting histone deacetylase (HDAC) inhibitors capable of regulating the signal transduction between RAS protein and downstream effectors were obtained by introducing a zinc-ion-binding group into the framework of rigosertib via different linkers. Among them, two representative compounds, XSJ-7 and XSJ-10, not only showed stronger antiproliferative activity against many types of cancer cells including solid tumor cells but also presented more potent inhibition on different subtypes of HDAC than suberoylanilide hydroxamic acid (SAHA). Significantly, XSJ-10 presented moderate pharmacokinetic behaviors and showed stronger antitumor activity than oxaliplatin, SAHA, and rigosertib in the HT-29 xenograft mouse models without significant systemic toxicity. Research on the anticancer mechanism of XSJ-10 revealed that it can effectively induce the apoptosis of cancer cells and suppress the tumor by strongly inhibiting the RAS-RAF-MEK-ERK signaling pathway and the acetylation level of HDAC3.
研究领域:
药理学
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肿瘤学
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分子生物学
✓ 已验证
DOI
高影响因子
Applied Nanoscience
·
2022
·Vol. 12
·期 12
·3883-3899
·
IF 3.869
Farooq Muhammad Umar,Sahin Yesim Muge,Naz Muhammad Yasin,Ijaz Salman,Shukrullah Shazia,Makhlouf Mohamed M.
A paradigm transition in cancer treatment gradually moved from "one drug-one target" toward "multi-target selective drugs design", because different drugs simultaneously inhibit tumor progression differently. The underlying mechanism has encountered significant challenges, such as encapsulating chemotherapies into a nanosized particulate system, adverse side effects, and managing multidrug-resistant. To address these issues, herein we engineered the gold nanoparticles’ surfaces with cross-linked polyethylene glycol that have well-controlled morphology and further encapsulated with commonly known chemo-drugs paclitaxel and bleomycin for nanovectorization of therapeutics to the intended site and there act through the concurrent action of dual targeting mechanisms without creating undesired side effects. The structures of the nanovectorization particulate system were confirmed by various spectroscopic techniques. The efficacy of nanovectorization particulate system and non-targeted free drugs was evaluated using the human cervical adenocarcinoma cell model. Our findings indicate that this nanovectorization particulate system had synergic stimuli-responsive characteristics and unrivaled control of efficient transportation of therapeutics agents. This system meets the high demand for multiple targeting delivery and has substantial benefits across multiple fields of nanomedicine, especially in chemotherapy.
研究领域:
纳米医学
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肿瘤学
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药剂学
✓ 已验证
产品关联
DOI
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2024
·
IF 4.2
Songxia Cheng,Jiali Ding,Biao Xu,Yan Wang,Xiaoyu Shen,Yanhua Xia,Lei Wu,Jie Wei
Burn induced-pain (BIP) is one of the most common pain symptoms, which seriously affects the quality of sufferer life. Researches show that multi-targeted drug therapies offer superior efficacy and fewer side effects compared to single-target drug therapies. Consequently, in this study, we developed G(1-5)-EM2, a multi-targeted peptide designed to target μ-opioid receptor and the growth hormone secretagogue receptor 1α (GHS-R1α), and explored its antinociceptive effects on burn injury pain. Calcium mobilization experiments revealed that G(1-5)-EM2 demonstrated weak multi-agonist activities to μ-opioid receptor and κ-opioid receptor as well as GHS-R1α in vitro. Near-infrared fluorescence imaging experiments demonstrated that G(1-5)-EM2 could penetrate the blood-brain barrier (BBB) and access the brain following intravenous injection. The enzymatic stability of G(1-5)-EM2 was significantly enhanced compared to EM2. Our results indicated that intrathecal administration of G(1-5)-EM2 mitigated mechanical allodynia and thermal hyperalgesia in BIP. These antinociceptive effects of G(1-5)-EM2 were partially mediated through μ-opioid receptor and GHS-R1α. Moreover, intrathecal administration of G(1-5)-EM2 significantly decreased burn-induced up-regulation of phosphorylated p38 MAPK, phosphorylated NF-κBp65 and TRPV1 in the ipsilateral spinal cord, reduced the levels of IL-1β, IL-6 and TNF-α in serum, and enhanced wound healing in burned skin. Repeated intrathecal administration of G(1-5)-EM2 produced a non-tolerance-forming antinociception in BIP. These results suggest that the multi-targeted peptide G(1-5)-EM2 exhibits a novel role in alleviating BIP with fewer side effects and may represent a promising strategy for developing new analgesic drugs.
研究领域:
药理学
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疼痛研究
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
PHYTOCHEMISTRY
·
2018
·
IF 3.186
Chun-Li Xia,Gui-Hua Tang,Yan-Qiong Guo,You-Kai Xu,Zhi-Shu Huang,Sheng Yin
Mulberry Diels-Alder-type adducts (MDAAs) are a group of structurally unique natural products biosynthetically derived from the intermolecular [4 + 2] cycloaddition of a dehydroprenylphenol and a chalcone . In the current study, ten MDAAs, including an undescribed one, inethermulberrofuran C, were isolated from the root bark of Morus alba . The anti-Alzheimer's disease (anti-AD) properties of these isolates were systematically screened for a series of potential targets (A β self-aggregation, tau aggregation, and ChEs) as well as the anti-neuroinflammatory and neuroprotective activities. Four compounds, mulberrofuran C, mulberrofuran K, mulberrofuran G, and isomulberrofuran G, turned out to be potent multi-targeted agents for AD. Among them, mulberrofuran K with a good blood-brain barrier (BBB) permeability (8.7 ± 0.3 × 10 −6 cm/s) was selected as a promising candidate for further mechanism study in glutamate-induced HT22 cell model, which showed its neuroprotective ability on up-regulation of the glutathione (GSH) level and suppression of the reactive oxygen species (ROS) production.
研究领域:
药理学
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植物化学
·
神经科学
✓ 已验证
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2023
·
IF 8.4
Rui Tian,Qi Yu,Li-Jun Mei,Feng-Yu Zhu,Qi Qin,Rongliang Ma,Ya-Long Wang,Chong Li,Ming-Qiang Zhu
Existing latent fingerprint developers achieve marvelous progress during the past decades. However, most of these methods mainly consider single target substance, which may face difficulties in latent fingerprint imaging when the corresponding substance is absent from latent fingerprint traces. To alleviate this issue, we propose a novel single-molecule multi-target green fluorescent probe , TPE-NI-NHS, which could target both lipids and amino acids through physical adsorption and chemically bonding under mild conditions, respectively. Specifically, tetraphenylethylene and active ester group in TPE-NI-NHS are connected at two ends of the naphthalimide core, which provide perfect aggregation-induced emission, accurate and quick reaction with amino acids, lipophilic properties , and green fluorescence emission . As expected, TPE-NI-NHS achieves green fluorescent imaging for latent fingerprints contained different contents of lipids and amino acids with high quality, high sensitivity, and high contrast under mild conditions. In summary, TPE-NI-NHS developer provides multiple targeting features, novel imaging principles and mild imaging process to latent fingerprint detections.
研究领域:
生物化学
·
法医学
✓ 已验证
产品关联
DOI
高影响因子
Journal of Advanced Research
·
2025
·
IF 13
Jia Xu,Bingxin Huangfu,Teng Wang,Xinxin Ren,Feng Zhang,Kunlun Huang,Xiaoyun He
Introduction The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) is rising, while current pharmacological treatments are often limited by adverse effects. Artemether (Art), a derivative of artemisinin, has demonstrated therapeutic potential against MAFLD, but its direct molecular targets remain unclear. Objectives This work focuses on Art’s therapeutic effects and molecular targets in MAFLD. Methods In this study, MAFLD was induced in C57BL/6J male mice via high-fat diets, followed by treatment with Art at 10 or 50 mg/kg·bw/d; obeticholic acid served as a positive control. Glucose tolerance, serum biochemistry, and liver histology were assessed. Fatty acid-induced MAFLD models in HepG2 and primary mouse hepatocytes were treated with Art (5 µM or 25 µM), and lipid accumulation was evaluated. Protein target identification involved drug affinity responsive target stability (DARTS), cellular thermal shift assay (CESTA), chemical proteomics, and molecular docking etc. Heat shock protein 90 (HSP90) and epidermal growth factor receptor (EGFR) were confirmed as direct targets of Art through over-expression, inhibition, and knockdown techniques in cells and mice. Results Art dose-dependently reduced hepatic lipid accumulation in MAFLD mice and suppressed oleic-palmitic acid–induced lipid droplet formation in vitro . HSP90 and EGFR were identified as direct binding targets of Art, which disrupted the HSP90–EGFR complex, reducing EGFR stability and expression. The therapeutic efficacy of Art was not further enhanced when administered following HSP90 or EGFR knockdown, confirming that HSP90 and EGFR function as key molecular targets of Art. Conclusion These findings identify EGFR as a key target of Art, modulated directly or via HSP90, thereby offering new insights into Art’s multi-target therapeutic mechanism in MAFLD.
研究领域:
药理学
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分子生物学
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肝病学
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生物化学
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药物研发
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN POLYMER JOURNAL
·
2025
·
IF 6.3
Bufan Li,Mou He,Jie Shen,Pengyan Zhang,Shaohua Wu,Yafei Wang,Wenwen Zhao
In recent years, diabetic wounds have garnered significant attention due to their challenging healing rates. Although numerous related dressings have been designed and developed, their limited therapeutic efficacy often fails to confront the complex pathological microenvironment. Our study constructed a multifunctional dressing by incorporating short fibers (SF) into hydrogels to form a biomimetic cell scaffold, namely MeGel-SF. Noticeably, hydrogels provided a three-dimensional microenvironment for cell adhesion and migration, and loaded SF enhanced the mechanical support of hydrogels while simulating the extracellular matrix meshwork. Moreover, Salvia miltiorrhiza Bunge-Radix Puerariae herbal compound (SR), famous traditional Chinese medicine and owing multi-activate characteristics, was loaded into MeGel-SF to demonstrate multi-target therapeutic advantages. The data from material characterisation proved that both MeGel and MeGel-SF SR exhibited excellent mechanical, water-retaining as well as hemostatic performances. In vivo, MeGel-SF SR patches showed a faster wound healing rate compared to control and MeGel groups, achieving a healing area of 89.7 ± 0.25 % at day 18 post-surgery. Furthermore, the MeGel-SF SR dressing patches significantly increased healing speed and improved quality of regenerated tissue in diabetic wounds by promoting hair follicle regeneration, collagen deposition, reducing inflammation, and encouraging vascularization. In all, our study demonstrated that the MeGel-SF SR dressing patches hold significant promise for treating hard-healing diabetic wounds in clinic.
研究领域:
生物材料学
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药理学
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医学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）