The extracellular polymeric substances (EPS) accumulation of Spirulina platensis responding to Cadmium (Cd2+) exposure.

Spirulina platensis can secrete extracellular polymeric substances (EPS) helping to protect damage from stress environment, such as cadmium (Cd2+) exposure. However, the responding mechanism of S. platensis and the secreted EPS to exposure of Cd2+ is still unclear. This research focuses on the effects of Cd2+ on the composition and structure of the EPS and the response mechanism of EPS secretion from S. platensis for Cd2+ exposure. S. platensis can produce 261.37 mg·g-1 EPS when exposing to 20 mg·L-1 CdCl2, which was 2.5 times higher than the control group. The S. platensis EPS with and without Cd2+ treatment presented similar and stable irregularly fibrous structure. The monosaccharides composition of EPS in Cd2+ treated group are similar with control group but with different monosaccharides molar ratios, especially for Rha, Gal, Glc and Glc-UA. And the Cd2+ treatment resulted in a remarkable decline of humic acid and fulvic acid content. The antioxidant ability of S. platensis EPS increased significantly when exposed to 20 mg·L-1 CdCl2, which could be helpful for S. platensis protecting damage from high concentration of Cd2+. The transcriptome analysis showed that sulfur related metabolic pathways were up-regulated significantly, which promoted the synthesis of sulfur-containing amino acids and the secretion of large amounts of EPS.

Brazilin-7-2-butenoate inhibits amyloid ß-protein aggregation, alleviates cytotoxicity, and protects Caenorhabditis elegans.

The fibrillogenesis of amyloid ß-protein (Aß) gradually accumulates to form neurotoxic Aß aggregates in the human brain, which is the direct cause of Alzheimer's disease (AD) related symptoms. There are currently no effective therapies for AD. Brazilin, a natural polyphenol, inhibits Aß fibrillogenesis, disrupts the mature fibrils and alleviates the corresponding cytotoxicity, but it also has the high toxic. Therefore, brazilin-7-2-butenoate (B-7-2-B), a brazilin derivative, was designed and synthesized. B-7-2-B exhibited lower toxicity and stronger inhibitory effect on Aß aggregation than brazilin. B-7-2-B could prevent the formation of Aß fibrils and oligomers, and depolymerize pre-formed aggregates in a dose-dependent manner. Furthermore, B-7-2-B prominently alleviated the cytotoxicity and the oxidative stress induced by Aß aggregates in PC12 cells. The protective impacts of B-7-2-B were further demonstrated by using the Caenorhabditis elegans model, including decreasing the extent of Aß aggregation, improving the motility and sensation disorders. Eventually, B-7-2-B was proven to be no apparent damage to worms. In summarize, it can be concluded that B-7-2-B has the potential as a drug for treating AD.

Activation of ERß hijacks the splicing machinery to trigger R-loop formation in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with aggressive behavior and poor prognosis. Current therapeutic options available for TNBC patients are primarily chemotherapy. With our evolving understanding of this disease, novel targeted therapies, including poly ADP-ribose polymerase (PARP) inhibitors, antibody-drug conjugates, and immune-checkpoint inhibitors, have been developed for clinical use. Previous reports have demonstrated the essential role of estrogen receptor ß (ERß) in TNBC, but the detailed molecular mechanisms downstream ERß activation in TNBC are still far from elucidated. In this study, we demonstrated that a specific ERß agonist, LY500307, potently induces R-loop formation and DNA damage in TNBC cells. Subsequent interactome experiments indicated that the residues 151 to 165 of U2 small nuclear RNA auxiliary factor 1 (U2AF1) and the Trp439 and Lys443 of ERß were critical for the binding between U2AF1 and ERß. Combined RNA sequencing and ribosome sequencing analysis demonstrated that U2AF1-regulated downstream RNA splicing of 5-oxoprolinase (OPLAH) could affect its enzymatic activity and is essential for ERß-induced R-loop formation and DNA damage. In clinical samples including 115 patients from The Cancer Genome Atlas (TCGA) and 32 patients from an in-house cohort, we found a close correlation in the expression of ESR2 and U2AF1 in TNBC patients. Collectively, our study has unraveled the molecular mechanisms that explain the therapeutic effects of ERß activation in TNBC, which provides rationale for ERß activation-based single or combined therapy for patients with TNBC.

Butin attenuates behavioral disorders via cholinergic/BDNF/Caspase-3 pathway in scopolamine-evoked memory deficits in rats.

OBJECTIVE: Recent research suggests that butin may also exert neuroprotective effects. However, its influence on cognitive performance and, specifically, its potential to mitigate scopolamine-induced memory impairment remains unexplored. The aim of the study is to investigate the effects of butin on the cognitive and behavioral performance of rats with scopolamine-induced memory impairment. MATERIALS AND METHODS: Scopolamine-injected memory-impediment model in rats was used to determine the efficacy of butin in higher and lower doses (10 and 20 mg/kg) for 14 days. Y-maze, along with Morris water, was used to assess the ability to recall spatial and working information. Biochemistry-related functions such as acetylcholinesterase, choline acetyltransferase, superoxide dismutase, glutathione transferase, malonaldehyde, catalase, nitric oxide, and neurotransmitters levels were estimated as indicators of free radical damage. Furthermore, we evaluated neuro-inflammatory responses by assessing tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1ß), interleukin-6 (IL-6), brain-derived neurotrophic factor (BDNF) and caspase-3 immuno-reactive proteins. RESULTS: When assessed through behavioral paradigms, the butin-treated group enhanced the spatial and working memory of rodents. Scopolamine caused a substantial alteration in biochemical-related parameters, neuronal enzymatic, inflammation responses and apoptosis markers prominently restored by butin. CONCLUSIONS: This study concludes that butin protects scopolamine-injected rats from behavioral impairments and neuronal damage by reducing apoptosis and neuroinflammation.

Design, synthesis and anticancer evaluation of some novel 7-hydroxy-4-methyl-3-substituted benzopyran-2-one derivatives.

Aim: 22 derivatives of 7-hydroxy-4-methyl-3-substituted benzopyran-2-one were designed, synthesized and evaluated for their anticancer activity. Materials & methods: The prepared compounds were screened for their cytotoxicity against the MCF-7 breast cancer cell line. The best five were then evaluated against MCF10a to check their safety and then tested for their PI3K and Akt-1 inhibitory action. The best two derivatives were further analyzed through cell cycle analysis, caspase 3/7 activation, increasing BAX level and decreasing BCL-2. Docking and absorption, distribution, metabolism and excretion prediction studies were also performed. Results & conclusion: Compounds 3b, 3c, 3j, 7 and 8 were the most active. Compounds 3c and 8 showed remarkable inhibitory action against PI3K and Akt-1 enzymes, and both are promising candidates for treatment of breast cancer.

Novel 4-Aryl-4H-chromene derivative displayed excellent in vivo anti-glioblastoma efficacy as the microtubule-targeting agent.

In this study, a series of novel 4-Aryl-4H-chromene derivatives (D1-D31) were designed and synthesized by integrating quinoline heterocycle to crolibulin template molecule based on the strategy of molecular hybridization. One of these compounds D19 displayed positive antiproliferative activity against U87 cancer cell line (IC50 = 0.90 ± 0.03 µM). Compound D19 was verified as the microtubule-targeting agent through downregulating tubulin related genes of U87 cells, destroying the cytoskeleton of tubulins and interacting with the colchicine-binding site to inhibit the polymerization of tubulins by transcriptome analysis, immune-fluorescence staining, microtubule dynamics and EBI competition assays as well as molecular docking simulations. Moreover, compound D19 induced G2/M phase arrest, resulted in cell apoptosis and inhibited the migration of U87 cells by flow cytometry analysis and wound healing assays. Significantly, compound D19 dose-dependently inhibited the tumor growth of orthotopic glioma xenografts model (GL261-Luc) and effectively prolonged the survival time of mice, which were extremely better than those of positive drug temozolomide (TMZ). Compound D19 exhibited potent in vivo antivascular activity as well as no observable toxicity. Furthermore, the results of in silico simulation studies and P-gp transwell assays verified the positive correlation between compound D19's Blood-Brain Barrier (BBB) permeability and its in vivo anti-GBM activity. Overall, compound D19 can be used as a promising anti-GBM lead compound for the treatment of glioblastoma.

Two undescribed benzopyran derivatives from Ranunculus sceleratus L. with their in vitro anti-inflammatory activity in lipopolysaccharide-activated RAW 264.7 cells.

Previous studies on Ranunculus sceleratus L. have shown the existence of coumarins and their anti-inflammatory effect. Phytochemical work was conducted to investigate the bioactive compounds, leading to the isolation of two undescribed benzopyran derivatives, namely ranunsceleroside A (1) and B (3), together with two known coumarins (2, 4) from the whole plant of R. sceleratus L. All compounds were structurally identified by extensive spectroscopic analysis and then investigated for their inhibitory effect on nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) production induced by lipopolysaccharide (LPS) in RAW 264.7 murine macrophages, repectively. As a result, compound 1-4 presented inhibitory effects on the production of NO, TNF-α, IL-1ß, and IL-6 in a concentration-dependent manner, which provides a potential chemical basis for the traditional use of R. sceleratus L. as an anti-inflammatory plant.

Indolyl-4H-Chromene Derivatives as Antibacterial Agents: Synthesis, in Vitro and in Silico Studies.

In this study, indolyl-4H-chromene derivatives are designed and synthesised using an eco-friendly multicomponent one-pot synthesis using benzaldehydes, nitroketene N, S-acetals, and indoles combine with InCl3 , a Lewis acid catalyst, and ethanol, an environmentally acceptable solvent. Due to antibiotic resistance, assessed these Indolyl-4H-chromene derivatives for their in vitro antibacterial activity against Gram-positive and Gram-negative bacteria, including Streptococcus pyogenes, Staphylococcus aureus, Clostridium pyrogenes, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa, using the agar well diffusion method and Minimum Inhibition Concentration (MIC) assay. Three compounds, 4-(1H-indol-3-yl)-6-methoxy-N-methyl-3-nitro-4H-chromen-2-amine, 4-(1H-indol-3-yl)-3-nitro-N-phenyl-4H-chromen-2-amine and 4-(6-Fluoro-1H-Indol-3-yl)-N-methyl-3-nitro-4H-chromen-2-amine showed better zone of inhibition (mm) and Minimum Inhibition Concentration (MIC) values of 10 µg/mL to 25 µg/mL against all bacterial types. The Ki values of 278.60 nM and 2.21 nM for compound 4-(1H-indol-3-yl)-3-nitro-N-phenyl-4H-chromen-2-amine showed improved interactions with DNA gyrase B and topoIV ParE's ATP binding sites in in silico studies.

Modulating SIRT1, Nrf2, and NF-κB signaling pathways by bergenin ameliorates the cadmium-induced nephrotoxicity in rats.

In light of the current industrial evolution, exposure to cadmium has become a significant public health concern. Cadmium accumulates in the renal tubular cells and causes nephrotoxicity largely through disruption of the redox homeostasis, induction of inflammation, and suppression of the histone deacetylase SIRT1 expression. The current work aimed at exploring the protective capability of bergenin, a naturally-occurring methyl gallic acid derivative, against the cadmium-evoked nephrotoxicity. Male Wistar rats were treated either with cadmium alone or with cadmium and bergenin for a 7-day experimental period followed by collection of kidney and blood specimens that were subjected to biochemical, molecular, and histological investigations. The results revealed the ability of bergenin to improve the renal functions in the cadmium-intoxicated rats as evidenced by increased glomerular filtration rate, and decreased serum creatinine and blood urea nitrogen. Equally important, bergenin reduced the renal tissue injury and enhanced its redox homeostasis as indicated by decreased protein expression of the kidney injury marker KIM-1, reduced lipid peroxidation, and improved antioxidant potential and histopathological picture of the renal tissues. Mechanistically, bergenin reduced the renal tissue cadmium content, markedly up-regulated protein expression of SIRT1 that regulates inflammation and the redox status of the renal tissues. Additionally, it improved the expression of the major antioxidant transcription factor Nrf2 and its responsive gene products heoxygenase-1 and NAD(P)H quinone dehydrogenase 1 in the cadmium-intoxicated rats. In the same context, bergenin down-regulated the acetylation and the nuclear translocation of the inflammatory transcription factor NF-κB and reduced levels of its responsive gene products TNF-α and IL-1ß, as well as the activity of the inflammatory cell infiltration biomarker myeloperoxidase. Collectively, the current study underscores the ameliorating activity of bergenin against the cadmium-evoked nephrotoxicity and highlights modulation of SIRT1, Nrf2, and NF-κB signaling as potential underlining molecular mechanisms.

Synthesis and biological evaluations of 8-biaryl-2,2-dimethylbenzopyranamide derivatives against Alzheimer's disease and ischemic stroke.

Alzheimer's disease, the commonest cause of dementia, is a growing global health concern with huge implications for individuals and society. Stroke has still been a significant challenge in clinics for a long time, which is the second leading cause of death in the world, especially ischemic stroke. Both Alzheimer's disease and stroke are closely related to oxidative stress and HIF-1 signaling pathways in nerve cells. Herein, we describe our structure-based design, synthesis, and biological evaluation of a new class of 8-biaryl-2,2-dimethylbenzopyranamide derivatives as natural product derivatives. Our efforts have resulted in the discovery of highly potent neuroprotective agents, as exemplified by compound D13 as a HIF-1α inhibitor, which significant improvement in the behavior of Alzheimer's disease mice and shows great potential improvement of brain infarct volume in pMCAO model rats, improves the increase of blood-brain barrier permeability after cerebral ischemia in rats, neuroprotective effect, reduce the level of apoptotic cells in rats after cerebral ischemia, better than Edaravone.

2H-chromene and 7H-furo-chromene derivatives selectively inhibit tumour associated human carbonic anhydrase IX and XII isoforms.

Tumour associated carbonic anhydrases (CAs) IX and XII have been recognised as potential targets for the treatment of hypoxic tumours. Therefore, considering the high pharmacological potential of the chromene scaffold as selective ligand of the IX and XII isoforms, two libraries of compounds, namely 2H-chromene and 7H-furo-chromene derivatives, with diverse substitution patterns were designed and synthesised. The structure of the newly synthesised compounds was characterised and their inhibitory potency and selectivity towards human CA off target isoforms I, II and cancer-associated CA isoforms IX and XII were evaluated. Most of the compounds inhibit CA isoforms IX and XII with no activity against the I and II isozymes. Thus, while the potency was influenced by the substitution pattern along the chromene scaffold, the selectivity was conserved along the series, confirming the high potential of both 2H-chromene and 7H-furo-chromene scaffolds for the design of isozyme selective inhibitors.

Benzopyrone-mediated quinolones as potential multitargeting antibacterial agents.

A new type of benzopyrone-mediated quinolones (BMQs) was rationally designed and efficiently synthesized as novel potential antibacterial molecules to overcome the global increasingly serious drug resistance. Some synthesized BMQs effectively suppressed the growth of the tested strains, outperforming clinical drugs. Notably, ethylidene-derived BMQ 17a exhibited superior antibacterial potential with low MICs of 0.5-2 µg/mL to clinical drugs norfloxacin, it not only displayed rapid bactericidal performance and inhibited bacterial biofilm formation, but also showed low toxicity toward human red blood cells and normal MDA-kb2 cells. Mechanistic investigation demonstrated that BMQ 17a could effectually induce bacterial metabolic disorders and promote the enhancement of reactive oxygen species to disrupt the bacterial antioxidant defense system. It was found that the active molecule BMQ 17a could not only form supramolecular complex with lactate dehydrogenase, which disturbed the biological functions, but also effectively embed into calf thymus DNA, thus affecting the normal function of DNA and achieving cell death. This work would provide an insight into developing new molecules to reduce drug resistance and expand antibacterial spectrum.

Novel quinazoline-chromene hybrids as anticancer agents: Synthesis, biological activity, molecular docking, dynamics and ADME studies.

In this study, new quinazoline-chromene hybrid compounds were synthesized. The cytotoxic effects on cell viability of the hybrid compounds were tested against A549 human lung adenocarcinoma and BEAS-2B healthy bronchial epithelial cell lines in vitro. In addition, the ability of the active compounds to inhibit cell migration was tested. Molecular docking studies were performed to evaluate the ligand-protein interactions, and molecular dynamics simulations were performed to determine the interactions and stability of ligand-protein complexes. In silico absorption, distribution, metabolism, and excretion (ADME) studies were conducted to estimate the drug-likeness of the compounds. Compounds 4 (IC50 = 51.2 µM) and 5 (IC50 = 44.2 µM) were found to be the most active agents against A549 cells. They are found to be more selective against A549 cells than the reference drug doxorubicin. They also have the ability to significantly inhibit cell migration. They have the best docking scores against epidermal growth factor receptor (EGFR) (-11.300 and -11.226 kcal/mol) and vascular endothelial growth factor receptor 2 (VEGFR2) (-10.987 and -11.247 kcal/mol), respectively. In MD simulations, compounds 4 and 5 have strong hydrogen bond interactions above 80% of simulation times and showed a low ligand root mean square deviation (RMSD) around 2 Å. According to the ADME analysis, compounds 4 and 5 exhibit excellent drug-likeness and pharmacokinetic characteristics.

Strategies for developing retinoic acid receptor alpha-selective antagonists as novel agents for male contraception.

Reported here are the synthesis and in vitro evaluation of a series of 26 retinoic acid analogs based on dihydronaphthalene and chromene scaffolds using a transactivation assay. Chromene amide analog 21 was the most potent and selective retinoic acid receptor α antagonist identified from this series. In vitro evaluation indicated that 21 has favorable physicochemical properties and a favorable pharmacokinetic PK profile in vivo with significant oral bioavailability, metabolic stability, and testes exposure. Compound 21 was evaluated for its effects on spermatogenesis and disruption of fertility in a mouse model. Oral administration of compound 21 at low doses showed reproducibly characteristic albeit modest effects on spermatogenesis, but no effects on fertility were observed in mating studies. The inhibition of spermatogenesis could not be enhanced by raising the dose and lengthening the duration of dosing. Thus, 21 may not be a good candidate to pursue further for effects on male fertility.

Synthesis and in Silico Study of Novel Benzisoxazole-Chromene Derivatives as Potent Inhibitors of Acetylcholinesterase: Metal-Free Site-Selective C-N Bond Formation via Aza-Michael Reaction.

An efficient metal-free approach for site selective C-N coupling reaction of benzo[d]isoxazole and 2H-chromene derivatives has been designed and developed against AchE. This nitrogen containing organo-base promoted methodology, which is both practical and environmentally friendly, provides an easy and suitable pathway for synthesizing Benzisoxazole-Chromene (BC) possessing poly heteroaryl moieties. The synthesized BC derivatives 4 a-n was docked into the active sites of AChE to obtain more perception into the binding modes of the compounds. Out of them, compound 4 a and 4 l displayed potent activity and high selectivity against the AChE inhibition. Final docking results indicates that compound 4 l showed the lowest binding energy of -11.2260 kcal/mol with AChE. The synthesized BC analogs would be potential candidates for promoting suitable studies in medicinal chemistry research.

Synthesis and Characterization of Novel 4-aryl-4H-chromene Derivatives using Borax and Evaluation of their Anticancer Effects.

BACKGROUND/INTRODUCTION: 4-aryl-4H-chromenes have attracted attention as potential anticancer agents. OBJECTIVE: In an effort to discover effective compounds, we designed a new series of these chromenes with methoxy substitution at 2, 3, 4, 5, and 6 positions. METHODS: The synthesized compounds were tested for anticancer properties against two human cancer cell lines (MCF- 7 and PC3) as well as a normal cell line. Furthermore, induction of apoptosis was explored through various methods, such as flow cytometry analysis, morphological changes, activation of caspase 3, ROS, and MMP. RESULTS: The MTT assay showed that the 5g derivative, with methoxy groups at ortho and meta positions, exhibited the highest potency (IC50 = 40 µM) against the PC3 cell line. Our findings revealed that compound 5g induced apoptosis in the PC3 cell line, which was demonstrated by activation of caspase 3, an increase in ROS levels, and early apoptosis percentage. CONCLUSION: These results suggest that compound 5g holds promise as a potential therapeutic approach to cancer treatment.

Design, Synthesis, and Antiproliferative Activity of Benzopyran-4-One-Isoxazole Hybrid Compounds.

The biological significance of benzopyran-4-ones as cytotoxic agents against multi-drug resistant cancer cell lines and isoxazoles as anti-inflammatory agents in cellular assays prompted us to design and synthesize their hybrid compounds and explore their antiproliferative activity against a panel of six cancer cell lines and two normal cell lines. Compounds 5a-d displayed significant antiproliferative activities against all the cancer cell lines tested, and IC50 values were in the range of 5.2-22.2 µM against MDA-MB-231 cancer cells, while they were minimally cytotoxic to the HEK-293 and LLC-PK1 normal cell lines. The IC50 values of 5a-d against normal HEK-293 cells were in the range of 102.4-293.2 µM. Compound 5a was screened for kinase inhibitory activity, proteolytic human serum stability, and apoptotic activity. The compound was found inactive towards different kinases, while it completely degraded after 2 h of incubation with human serum. At 5 µM concentration, it induced apoptosis in MDA-MB-231 by 50.8%. Overall, these findings suggest that new benzopyran-4-one-isoxazole hybrid compounds, particularly 5a-d, are selective anticancer agents, potentially safe for human cells, and could be synthesized at low cost. Additionally, Compound 5a exhibits potential anticancer activity mediated via inhibition of cancer cell proliferation and induction of apoptosis.

Norbergenin prevents LPS-induced inflammatory responses in macrophages through inhibiting NFκB, MAPK and STAT3 activation and blocking metabolic reprogramming.

Inflammation is thought to be a key cause of many chronic diseases and cancer. However, current therapeutic agents to control inflammation have limited long-term use potential due to various side-effects. This study aimed to examine the preventive effects of norbergenin, a constituent of traditional anti-inflammatory recipes, on LPS-induced proinflammatory signaling in macrophages and elucidate the underlying mechanisms by integrative metabolomics and shotgun label-free quantitative proteomics platforms. Using high-resolution mass spectrometry, we identified and quantified nearly 3000 proteins across all samples in each dataset. To interpret these datasets, we exploited the differentially expressed proteins and conducted statistical analyses. Accordingly, we found that LPS-induced production of NO, IL1ß, TNFα, IL6 and iNOS in macrophages was alleviated by norbergenin via suppressed activation of TLR2 mediated NFκB, MAPKs and STAT3 signaling pathways. In addition, norbergenin was capable of overcoming LPS-triggered metabolic reprogramming in macrophages and restrained the facilitated glycolysis, promoted OXPHOS, and restored the aberrant metabolites within the TCA cycle. This is linked to its modulation of metabolic enzymes to support its anti-inflammatory activity. Thus, our results uncover that norbergenin regulates inflammatory signaling cascades and metabolic reprogramming in LPS stimulated macrophages to exert its anti-inflammatory potential.

Brazilin Inhibits the Invasion and Metastasis of Breast Cancer.

This study aimed to determine the effect of brazilin on the invasion and metastasis of breast cancer. The breast cancer MDA-MB-231 and 4T1 cells were treated with brazilin to investigate proliferation and invasion using cell proliferation assay, wound healing assay, transwell assay. BALB/C mice were randomized into normal, model, positive control, and Sappan L. extract groups (n = 6/group). The mice were injected with 4T1 cells via caudal veins to establish a lung metastasis model and via subcutaneous injection to establish a xenograft model. Metastatic nodules on the lung surface, survival rates and visceral indices were evaluated. Subcutaneous tumor volumes and weights were measured. Brazilin inhibited the proliferation of breast cancer cells and significantly inhibited the wound healing, migration, and invasion of MDA-MB-231 and 4T1 cells. Compared with the normal group, the average survival days and spleen index in the model group were significantly decreased, but the lung index and number of pulmonary metastatic nodules were significantly increased. Compared with the model group, the average survival and spleen index of dose groups were significantly increased, and the lung index, the number of pulmonary metastatic nodules, and tumor volume and weight were significantly decreased. Brazilin significantly inhibits the proliferation and metastasis of breast cancer. This study might suggest a new therapeutic agent for breast cancer.

Blockade of ß-Adrenergic Receptors by Nebivolol Enables Tumor Control Potential for Uveal Melanoma in 3D Tumor Spheroids and 2D Cultures.

Uveal melanoma (UM) is the most common primary cancer of the eye in adults. A new systemic therapy is needed to reduce the high metastasis and mortality rate. As ß-blockers are known to have anti-tumor effects on various cancer entities, this study focuses on investigating the effect of ß1-selective blockers atenolol, celiprolol, bisoprolol, metoprolol, esmolol, betaxolol, and in particular, nebivolol on UM. The study was performed on 3D tumor spheroids as well as 2D cell cultures, testing tumor viability, morphological changes, long-term survival, and apoptosis. Flow cytometry revealed the presence of all three ß-adrenoceptors with a dominance of ß2-receptors on cell surfaces. Among the blockers tested, solely nebivolol concentration-dependently decreased viability and altered 3D tumor spheroid structure. Nebivolol blocked the repopulation of cells spreading from 3D tumor spheroids, indicating a tumor control potential at a concentration of ≥20 µM. Mechanistically, nebivolol induced ATP depletion and caspase-3/7 activity, indicating that mitochondria-dependent signaling is involved. D-nebivolol or nebivolol combined with the ß2-antagonist ICI 118.551 displayed the highest anti-tumor effects, suggesting a contribution of both ß1- and ß2-receptors. Thus, the present study reveals the tumor control potential of nebivolol in UM, which may offer a perspective for co-adjuvant therapy to reduce recurrence or metastasis.