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Design, synthesis, and biological evaluation of cycloarylchalcone derivatives as microtubule inhibitors targeting breast cancer cells.

AIM: The increasing burden of breast cancer and drug resistance highlights the need for new chemotherapeutic agents. This study aimed to design and evaluate novel cycloarylchalcone derivatives as potential anticancer candidates targeting microtubules. MATERIALS & METHODS: A series of cycloarylchalcone derivatives containing a cyclohexenone core (CY1-10) were synthesized via Claisen-Schmidt condensation followed by Michael addition. Structural variations at the R and R1 positions were introduced to optimize activity. The cytotoxicity of the compounds was evaluated against MCF-7 and MDA-MB-231

4,4'-Dimethoxychalcone ameliorates estrogen-deficient osteoporosis by targeting PTP1B to inhibit the c-Src/NFATc1 signaling axis.

Postmenopausal osteoporosis (PMOP) is a skeletal disease linked to immune dysregulation, characterized by the overactivation of myeloid-lineage osteoclasts. To address the limitations of current therapies, this study investigated the immunomodulatory potential and molecular mechanism of the natural flavonoid 4,4'-dimethoxychalcone (DMC). Using in vitro and in vivo models, we found that DMC exhibited a desirable dual-action profile, potently inhibiting osteoclast differentiation while also promoting osteogenesis. Mechanistically, we identified Protein Tyrosine Phosphatase 1B (PTP1B) as a novel,

Butein inhibits NF-κB, AP-1 and Akt activation in adult T-cell leukemia/lymphoma.

Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia/lymphoma (ATLL) but there is no effective treatment for HTLV-1-associated diseases. Herein, we determined the effect of butein, a bioactive plant polyphenol, on cell growth, apoptosis and signaling pathways in HTLV-1-infected T-cell lines and on tumor growth in SCID mice. Treatment with butein caused a decrease in viability of HTLV-1-infected T-cell lines. T cells cultured with butein showed obvious apoptosis morphology, and cleavage of poly(ADP-ribose) polymerase with activation of caspase-3, -8 and -9

CX-F9, a novel RSK2 inhibitor, suppresses cutaneous melanoma cells proliferation and metastasis through regulating autophagy.

Approximately 60% of melanoma have BRAF mutation which leads to the abnormal activation of MAPK signaling pathway. Therefore, targeting these signaling pathways is particularly important for melanoma therapy. Ribosomal S6 Kinase 2 (RSK2) is a downstream target of ERK1/2 in MAPK/ERK pathway and inhibition of RSK2 suppresses the tumorigenesis and metastasis of neoplasm. We investigated whether CX-F9, a novel RSK2 inhibitor predicted by computer, inhibits the malignant phenotype of melanoma cells. In this study, we found knockdown of RSK2 expression in melanoma cells induces autophagy and inhibit

Oxyfadichalcone C inhibits melanoma A375 cell proliferation and metastasis via suppressing PI3K/Akt and MAPK/ERK pathways.

AIMS: Melanoma remains to be one of the most incurable cancers. Discovery of novel antitumor agent for melanoma therapy is expected. We recently isolated Oxyfadichalcone C from Oxytropis falcate and investigated the anti-proliferative and anti-metastatic activity on human melanoma A375 cells in vitro. MAIN METHODS: Cell viability was determined using MTT assay and soft agar cloning formation assay. The effect of Oxyfadichalcone C on cell cycle distribution and apoptosis were analyzed by flow cytometry. Cell metastasis was determined by wound healing assay, Transwell assay and Gelatin zymograp

Carthamin Yellow Protects the Heart Against Ischemia/Reperfusion Injury With Reduced Reactive Oxygen Species Release and Inflammatory Response.

Carthamin yellow (CY) is a flavonoid compound isolated from safflower, which is widely used clinically in China. It has various pharmacological effects including promoting blood circulation to remove blood stasis and alleviating pain. Ischemic heart disease is one of the main culprits of illness and death. Here, in this study, ex vivo and in vivo models were used to investigate whether CY reduces ischemia/reperfusion injury. In vitro experiments further verify and explain the potential mechanisms of CY cardioprotective function. Isolated hearts from male rats with or without CY pretreatment be

Isoliquiritigenin Attenuates UUO-Induced Renal Inflammation and Fibrosis by Inhibiting Mincle/Syk/NF-Kappa B Signaling Pathway.

PURPOSE: Chronic kidney disease (CKD) is a global nephrotic syndrome characterized by chronic inflammation, oxidative stress and fibrosis in the kidney. Isoliquiritigenin (ISL), a flavonoid from licorice, has historically been reported to inhibit innate immune responses to inflammation and fibrosis in vivo. However, the effect of ISL on CKD progression is largely unknown. MATERIALS AND METHODS: In this study, we employed the inflammatory and fibrotic models of LPS/TGF-β-induced bone marrow-derived macrophages (BMDM) in vitro and unilateral ureteral obstruction (UUO) model in vivo to explore t

Validity of biopsy-based drug effects in a diet-induced obese mouse model of biopsy-confirmed NASH.

BACKGROUND: Compounds in clinical development for nonalcoholic steatohepatitis (NASH) improve liver histopathology in diet-induced obese mouse models of biopsy-confirmed NASH. Since the biopsy section used for histopathological evaluation represents only < 1% of the whole mouse liver, we evaluated how well biopsy-based quantitative image analyses correlate to stereology-based whole-liver quantitative changes upon drug treatment. METHODS: Male leptin-deficient Lepob/Lepob mice were fed the Amylin liver NASH (AMLN) diet for 16 weeks before stratification into treatment groups using a biopsy-bas

Multidrug resistance reversal effect of DMC derived from buds of Cleistocalyx operculatus in human hepatocellular tumor xenograft model.

BACKGROUND: Multidrug resistance (MDR) is a major obstacle in the chemotherapeutic treatment of many human cancers. 2',4'-Dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC) isolated from the buds of Cleistocalyx operculatus (Roxb.) Merr. et Perry (Myrtaceae), was investigated for its reversal effects on cancer cell MDR. RESULTS: A human hepatocellular tumor xenograft model was established with the BEL-7402/5-FU cell line. Combined 5-fluorouracil (5-FU) and DMC (40 mg kg(-1) ) treatment significantly elevated tumor inhibition rate to 72.2%. DMC could also increase 5-FU concentrations in tumor t

Dual COX-2/TNF-α Inhibitors as Promising Anti-inflammatory and Cancer Chemopreventive Agents: A Review.

Cyclooxygenases (COX) play a pivotal role in inflammation and are responsible for the production of prostaglandins (PGs). Two types of COXs have been identified as key biological targets for drug design: Constitutive COX-1 and inducible COX-2. Nonsteroidal anti-inflammatory drugs (NSAIDs) target COX-1, while selective COX-2 inhibitors are designed for COX-2. These COX isoforms are involved in multiple physiological and pathological pathways throughout the body. Overproduction of tumor necrosis factor-alpha (TNF-α) plays a role in COX-2's inflammatory activity. Tumor necrosis factor-alpha can c

Совпадение в полном тексте источника
… Phenyl-pyrazoline-coumarin analog 48 Chalcones, precursors of flavonoids and isoflavonoids, can act on various drug targets such as COX-2 and TNF-α. … The key pharmacophore of chalcone analogs is their core, an α, β-unsaturated carbonyl-containing scaffold, which preferentially inhibits COX-2. …

Pharmacological Therapies for the Management of Inflammatory Bone Resorption in Periodontal Disease: A Review of Preclinical Studies.

Periodontitis, a highly prevalent multicausal chronic inflammatory and destructive disease, develops as a result of complex host-parasite interactions. Dysbiotic bacterial biofilm in contact with the gingival tissues initiates a cascade of inflammatory events, mediated and modulated by the host's immune response, which is characterized by increased expression of several inflammatory mediators such as cytokines and chemokines in the connective tissue. If periodontal disease (PD) is left untreated, it results in the destruction of the supporting tissues around the teeth, including periodontal li

Совпадение в полном тексте источника
… Chalcones Chalcone is a medicinal plant that has been conventionally used in Brazilian medicine to treat bleeding gums [ 130 ]. It is a phenolic compound extracted from the Myracrodruon urundeuva (Engl.). … Chalcone T4, a novel chalconic compound, inhibits inflammatory bone resorption in vivo and suppresses osteoclastogenesis in vitro. J Periodontal Res . 2021;53(3):569–578. doi: 10.1111/jre.12857. 48. Wei W., Ren J., Yin W., et al. …

Current Perspectives of the Applications of Polyphenols and Flavonoids in Cancer Therapy.

The development of anticancer therapies that involve natural drugs has undergone exponential growth in recent years. Among the natural compounds that produce beneficial effects on human health, polyphenols have shown potential therapeutic applications in cancer due to their protective functions in plants, their use as food additives, and their excellent antioxidant properties. The possibility of combining conventional drugs-which are usually more aggressive than natural compounds-with polyphenols offers very valuable advantages such as the building of more efficient anticancer therapies with l

Совпадение в полном тексте источника
… Chalcones Chalcones are a class of polyphenolic compounds that are characterized by the presence of an aromatic ketone and an enone in their central core. … A Review on Natural Chalcones An Update. Int. J. Pharm. Sci. Res. 2020;11:546–555. 142. Gómez-Rivera A., Aguilar-Mariscal H., Romero-Ceronio N., Roa-de la Fuente L.F., Lobato-García C.E. Synthesis and Anti-Inflammatory Activity of Three Nitro Chalcones. Bioorg. Med. Chem. …

Synergistic Anti-Inflammatory Effects of Dibenzoylmethane and Silibinin: Insights From LPS-Induced RAW 264.7 Cells and TPA-Induced Mouse Model.

Inflammation is an important predisposing factor for many chronic diseases. The dietary flavonoid silibinin (SB) has excellent anti-inflammatory properties in cells, but its low bioavailability in the blood compromises its therapeutic potential. This study aims to investigate the potential of dibenzoylmethane (DBM) to synergistically enhance the anti-inflammatory benefits of SB. The synergistic effects of DBM and SB in combination were evaluated in lipopolysaccharide (LPS)-induced RAW264.7 cells and 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced mice. In addition, a network pharmacology ap

Hydroxysafflor yellow A exerts anti-fibrotic and anti-angiogenic effects through miR-29a-3p/PDGFRB axis in liver fibrosis.

BACKGROUND: Liver fibrosis is a prevalent pathological process in chronic liver diseases characterized by excessive extracellular matrix (ECM) deposition and abnormal angiogenesis. Notably, hepatic stellate cells (HSCs) are the primary source of ECM. Activated HSCs not only secrete numerous pro-fibrotic cytokines but also are endowed with a pro-angiogenic phenotype to promote pathological angiogenesis. Therefore, targeted modulation of HSCs has emerged as a pivotal strategy for addressing liver fibrosis. Hydroxysafflor yellow A (HSYA) is a homology of medicine and food colourant with good phar

Protective Effect of Hydroxysafflor Yellow A against Chronic Mild Stress-induced Memory Impairments by Suppressing Tau Phosphorylation in Mice.

Chronic stress plays a critical role in the etiology of sporadic Alzheimer's disease (AD). However, there are currently no effective drugs that can target chronic stress to prevent AD. In this study, we explored the neuroprotective effect of hydroxysafflor yellow A (HSYA) against chronic mild stress (CMS)-induced memory impairments in mice and the underlying mechanism. The Morris water maze test showed that HSYA significantly reduced CMS-induced learning and memory impairments in mice. HSYA increased the expression of brain-derived neurotrophic factor (BDNF) and activated downstream tropomyosi

Inhibition of COX-2, mPGES-1 and CYP4A by isoliquiritigenin blocks the angiogenic Akt signaling in glioma through ceRNA effect of miR-194-5p and lncRNA NEAT1.

BACKGROUND: Arachidonic acid (AA) metabolic enzymes including cyclooxygenase-2 (COX-2), microsomal prostaglandin E synthase-1 (mPGES-1) and cytochrome P450 (CYP) 4A11 play important roles in glioma angiogenesis. Thus, there is an urgent need to identify the underlying mechanisms and develop strategies to overcome them. METHODS: A homology model of human CYP4A11 was constructed using SYBYL-X 2.0. Structure-based virtual screening against COX-2, mPGES-1 and CYP4A11was performed using the Surflex-Dock of the SYBYL suite. The candidates were further evaluated their antiangiogenic activities in a

Hydroxysafflor yellow A actives BKCa channels and inhibits L-type Ca channels to induce vascular relaxation.

Hydroxy-safflor yellow A (HSYA) can exert a variety of effects upon the vascular system. However, the underlying mechanisms are not clear. The present study is to investigate its vasodilating effect and the mechanisms. Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) were enrolled for studying effects of HSYA on blood pressure, vasodilation, intracellular Ca2+ transient and membrane ion channels. Vasodilation and intracellular Ca2+ transient were measured by using vasomotor assay and fluorescence imaging system, respectively. The effect of HSYA on the large conductance Ca2+ ac

Nucleolin mediated pro-angiogenic role of Hydroxysafflor Yellow A in ischaemic cardiac dysfunction: Post-transcriptional regulation of VEGF-A and MMP-9.

Hydroxysafflor Yellow A (HSYA), a most representative ingredient of Carthamus tinctorius L., had long been used in treating ischaemic cardiovascular diseases in China and exhibited prominently anticoagulant and pro-angiogenic activities, but the underlying mechanisms remained largely unknown. This study aimed to further elucidate the pro-angiogenic effect and mechanism of HSYA on ischaemic cardiac dysfunction. A C57 mouse model of acute myocardial infarction (AMI) was firstly established, and 25 mg/kg HSYA was intraperitoneally injected immediately after operation and given once, respectively,

Hydroxysafflor yellow A alleviates myocardial ischemia/reperfusion in hyperlipidemic animals through the suppression of TLR4 signaling.

Hyperlipidemia aggravates myocardial ischemia/reperfusion (MI/R) injury through stimulating excessive inflammatory response. Therefore, blockade of inflammatory signal is a potential therapeutic management for MI/R complicated with hyperlipidemia. Hydroxysafflor yellow A (HSYA, a monomer extracted from Carthamus tinctorius L.), was studied in this article to address that the regulation of inflammatory signal would alleviate MI/R combined with hyperlipidemia injury. High-fat diet induced hyperlipidemia worsened MI/R mediated heart injury (elevation of infarct size, CK-MB and LDH activity), acti

Expression of chemokine CXCL12 and its receptor CXCR4 in folliculostellate (FS) cells of the rat anterior pituitary gland: the CXCL12/CXCR4 axis induces interconnection of FS cells.

The anterior pituitary gland is composed of five types of hormone-producing cells plus folliculostellate (FS) cells, which do not produce classical anterior pituitary hormones. FS cells are interconnected by cytoplasmic processes and encircle hormone-producing cells or aggregate homophilically. Using living-cell imaging of primary culture, we recently reported that some FS cells precisely extend their cytoplasmic processes toward other FS cells and form interconnections with them. These phenomena suggest the presence of a chemoattractant factor that facilitates the interconnection. In this stu