Unveilling genetic profiles and correlations of biofilm-associated genes, quorum sensing, and antibiotic resistance in Staphylococcus aureus isolated from a Malaysian Teaching Hospital.

BACKGROUND: Staphylococcus aureus is a notorious multidrug resistant pathogen prevalent in healthcare facilities worldwide. Unveiling the mechanisms underlying biofilm formation, quorum sensing and antibiotic resistance can help in developing more effective therapy for S. aureus infection. There is a scarcity of literature addressing the genetic profiles and correlations of biofilm-associated genes, quorum sensing, and antibiotic resistance among S. aureus isolates from Malaysia. METHODS: Biofilm and slime production of 68 methicillin-susceptible S. aureus (MSSA) and 54 methicillin-resistant (MRSA) isolates were determined using a a plate-based crystal violet assay and Congo Red agar method, respectively. The minimum inhibitory concentration values against 14 antibiotics were determined using VITEK® AST-GP67 cards and interpreted according to CLSI-M100 guidelines. Genetic profiling of 11 S. aureus biofilm-associated genes and agr/sar quorum sensing genes was performed using single or multiplex polymerase chain reaction (PCR) assays. RESULTS: In this study, 75.9% (n = 41) of MRSA and 83.8% (n = 57) of MSSA isolates showed strong biofilm-forming capabilities. Intermediate slime production was detected in approximately 70% of the isolates. Compared to MSSA, significantly higher resistance of clindamycin, erythromycin, and fluoroquinolones was noted among the MRSA isolates. The presence of intracellular adhesion A (icaA) gene was detected in all S. aureus isolates. All MSSA isolates harbored the laminin-binding protein (eno) gene, while all MRSA isolates harbored intracellular adhesion D (icaD), clumping factors A and B (clfA and clfB) genes. The presence of agrI and elastin-binding protein (ebpS) genes was significantly associated with biofilm production in MSSA and MRSA isolates, respectively. In addition, agrI gene was also significantly correlated with oxacillin, cefoxitin, and fluoroquinolone resistance. CONCLUSIONS: The high prevalence of biofilm and slime production among MSSA and MRSA isolates correlates well with the detection of a high prevalence of biofilm-associated genes and agr quorum sensing system. A significant association of agrI gene was found with cefoxitin, oxacillin, and fluoroquinolone resistance. A more focused approach targeting biofilm-associated and quorum sensing genes is important in developing new surveillance and treatment strategies against S. aureus biofilm infection.

Synthesis and Staphylococcus aureus biofilm inhibitory activity of indolenine-substituted pyrazole and pyrimido[1,2-b]indazole derivatives.

Staphylococcus aureus is a highly adaptable opportunistic pathogen that can form biofilms and generate persister cells, leading to life-threatening infections that are difficult to treat with antibiotics alone. Therefore, there is a need for an effective S. aureus biofilm inhibitor to combat this public health threat. In this study, a small library of indolenine-substituted pyrazoles and pyrimido[1,2-b]indazole derivatives were synthesised, of which the hit compound exhibited promising antibiofilm activities against methicillin-susceptible S. aureus (MSSA ATCC 29213) and methicillin-resistant S. aureus (MRSA ATCC 33591) at concentrations significantly lower than the planktonic growth inhibition. The hit compound could prevent biofilm formation and eradicate mature biofilms of MSSA and MRSA, with a minimum biofilm inhibitory concentration (MBIC50) value as low as 1.56 µg/mL and a minimum biofilm eradication concentration (MBEC50) value as low as 6.25 µg/mL. The minimum inhibitory concentration (MIC) values of the hit compound against MSSA and MRSA were 50 µg/mL and 25 µg/mL, respectively, while the minimum bactericidal concentration (MBC) values against MSSA and MRSA were > 100 µg/mL. Preliminary structure-activity relationship analysis reveals that the fused benzene ring and COOH group of the hit compound are crucial for the antibiofilm activity. Additionally, the compound was not cytotoxic to human alveolar A549 cells, thus highlighting its potential as a suitable candidate for further development as a S. aureus biofilm inhibitor.

Evaluation of Folate-Functionalized Nanoparticle Drug Delivery Systems-Effectiveness and Concerns.

Targeting folate receptors is a potential solution to low tumor selectivity concerning conventional chemotherapeutics. Apart from antibody-drug conjugates, folate-functionalized nanoparticle drug delivery systems are interesting to be explored due to many advantages, yet currently, none seems to enter the clinical trials. Multiple in vitro evidence is available to support its efficacy compared to the non-targeting carrier and free drug formulation. Additionally, several studies pointed out factors affecting its effectiveness, including surface properties and endosomal trapping. However, in vivo biodistribution studies revealed issues that may arise from folate receptor targeting, including rapid liver uptake, subsequently reducing the nanoparticles' tumor uptake. This issue may be due to the folate receptor ß expressed by the activated macrophages in the liver; route of administration and tumor location might also influence the targeting effectiveness. Moreover, it is perplexing to generalize nanoparticles reported from various publications, primarily due to the different formulations, lack of characterization, and experimental settings, making it harder to determine the accurate factor influencing targeting effectiveness.

Effects of Alkoxy Chain Length and 1-Hydroxy Group on Anticolorectal Cancer Activity of 2-Bromoalkoxyanthraquinones.

BACKGROUND: KRAS and p53 are two of the most common genetic alterations associated with colorectal cancer. New drug development targeting these mutated genes in colorectal cancer may serve as a potential treatment avenue to the current regimen. OBJECTIVE: The objective of the present study was to investigate the effects of alkoxy chain length and 1-hydroxy group on anticolorectal cancer activity of a series of 2-bromoalkoxyanthraquinones and corroborate it with their in silico properties. METHODS: In vitro anticancer activity of 2-bromoalkoxyanthraquinones was evaluated against HCT116, HT29, and CCD841 CoN cell lines, respectively. Molecular docking was performed to understand the interactions of these compounds with putative p53 and KRAS targets (7B4N and 6P0Z). RESULTS: 2-Bromoalkoxyanthraquinones with the 1-hydroxy group were proven to be more active than the corresponding counterparts in anticancer activity. Among the tested compounds, compound 6b with a C3 alkoxy chain exhibited the most promising antiproliferation activity against HCT116 cells (IC50 = 3.83 ± 0.05 µM) and showed high selectivity for HCT116 over CCD841 CoN cells (SI = 45.47). The molecular docking reveals additional hydrogen bonds between the 1-hydroxy group of 6b and the proteins. Compound 6b has adequate lipophilicity (cLogP = 3.27) and ligand efficiency metrics (LE = 0.34; LLE = 2.15) close to the proposed acceptable range for an initial hit. CONCLUSION: This work highlights the potential of the 1-hydroxy group and short alkoxy chain on anticolorectal cancer activity of 2-bromoalkoxyanthraquinones. Further optimisation may be warranted for compound 6b as a therapeutic agent against colorectal cancer.

Chitosan and its derivatives as polymeric anti-viral therapeutics and potential anti-SARS-CoV-2 nanomedicine.

The coronavirus pandemic, COVID-19 has a global impact on the lives and livelihoods of people. It is characterized by a widespread infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), where infected patients may develop serious medical complications or even face death. Development of therapeutic is essential to reduce the morbidity and mortality of infected patients. Chitosan is a versatile biomaterial in nanomedicine and exhibits anti-microbial, anti-cancer and immunomodulatory properties. This review highlights the progress in chitosan design and application pertaining to the anti-viral effects of chitosan and chitosan derivatives (hydroxypropyl trimethylammonium, sulfate, carboxymethyl, bromine, sialylglycopolymer, peptide and phosphonium conjugates) as a function of molecular weight, degree of deacetylation, type of substituents and their degree and site of substitution. The physicochemical attributes of these polymeric therapeutics are identified against the possibility of processing them into nanomedicine which can confer a higher level of anti-viral efficacy. The designs of chitosan for the purpose of targeting SARS-CoV-2, as well as the ever-evolving strains of viruses with a broad spectrum anti-viral activity to meet pandemic preparedness at the early stages of outbreak are discussed.

Nanoscaled PAMAM Dendrimer Spacer Improved the Photothermal-Photodynamic Treatment Efficiency of Photosensitizer-Decorated Confeito-Like Gold Nanoparticles for Cancer Therapy.

A critical factor in developing an efficient photosensitizer-gold nanoparticle (PS-AuNP) hybrid system with improved plasmonic photosensitization is to allocate a suitable space between AuNPs and PS. Poly(amidoamine) (PAMAM) dendrimer is selected as a spacer between the PS and confeito-like gold nanoparticles (confeito-AuNPs), providing the required distance (≈2.5-22.5 nm) for plasmon-enhanced singlet oxygen generation and heat production upon 638-nm laser irradiation and increase the cellular internalization of the nanoconjugates. The loading of the PS, tetrakis(4-carboxyphenyl) porphyrin (TCPP), and modified zinc phthalocyanine (ZnPc1) onto PAMAM-confeito-AuNPs demonstrate better in vitro cancer cell-killing efficacy, as the combined photothermal-photodynamic therapies (PTT-PDTs) outperforms the single treatment modalities (PTT or PDT alone). These PS-PAMAM-confeito-AuNPs also demonstrate higher phototoxicity than photosensitizers directly conjugated to confeito-AuNPs (TCPP-confeito-AuNPs and ZnPc1-confeito-AuNPs) against all breast cancer cell lines tested (MDA-MB-231, MCF7, and 4T1). In the in vivo studies, TCPP-PAMAM-confeito-AuNPs are biocompatible and exhibit a selective tumor accumulation effect, resulting in higher antitumor efficacy than free TCPP, PAMAM-confeito-AuNPs, and TCPP-confeito-AuNPs. In vitro and in vivo evaluations confirm PAMAM effectiveness in facilitating cellular uptake, plasmon-enhanced singlet oxygen and heat generation. In summary, this study highlights the potential of integrating a PAMAM spacer in enhancing the plasmon effect-based photothermal-photodynamic anticancer treatment efficiency of PS-decorated confeito-AuNPs.

Challenges and Complications of Poly(lactic-co-glycolic acid)-Based Long-Acting Drug Product Development.

Poly(lactic-co-glycolic acid) (PLGA) is one of the preferred polymeric inactive ingredients for long-acting parenteral drug products that are constituted of complex formulations. Despite over 30 years of use, there are still many challenges faced by researchers in formulation-related aspects pertaining to drug loading and release. Until now, PLGA-based complex generic drug products have not been successfully developed. The complexity in developing these generic drug products is not just due to their complex formulation, but also to the manufacturing process of the listed reference drugs that involve PLGA. The composition and product attributes of commercial PLGA formulations vary with the drugs and their intended applications. The lack of standard compendial methods for in vitro release studies hinders generic pharmaceutical companies in their efforts to develop PLGA-based complex generic drug products. In this review, we discuss the challenges faced in developing PLGA-based long-acting injectable/implantable (LAI) drug products; hurdles that are associated with drug loading and release that are dictated by the physicochemical properties of PLGA and product manufacturing processes. Approaches to overcome these challenges and hurdles are highlighted specifically with respect to drug encapsulation and release.

Analogues of 2'-hydroxychalcone with modified C4-substituents as the inhibitors against human acetylcholinesterase.

A series of C4-substituted tertiary nitrogen-bearing 2'-hydroxychalcones were designed and synthesised based on a previous mixed type acetylcholinesterase inhibitor. Majority of the 2'-hydroxychalcone analogues displayed a better inhibition against acetylcholinesterase (AChE) than butyrylcholinesterase (BuChE). Among them, compound 4c was identified as the most potent AChE inhibitor (IC50: 3.3 µM) and showed the highest selectivity for AChE over BuChE (ratio >30:1). Molecular docking studies suggested that compound 4c interacts with both the peripheral anionic site (PAS) and catalytic anionic site (CAS) regions of AChE. ADMET analysis confirmed the therapeutic potential of compound 4c based on its blood-brain barrier penetrating. Overall, the results suggest that this 2'-hydroxychalcone deserves further investigation into the therapeutic lead for Alzheimer's disease (AD).

A review on chitosan and its development as pulmonary particulate anti-infective and anti-cancer drug carriers.

Chitosan, as a biodegradable and biocompatible polymer, is characterized by anti-microbial and anti-cancer properties. It lately has received a widespread interest for use as the pulmonary particulate backbone materials of drug carrier for the treatment of infectious disease and cancer. The success of chitosan as pulmonary particulate drug carrier is a critical interplay of their mucoadhesive, permeation enhancement and site/cell-specific attributes. In the case of nanocarriers, various microencapsulation and micro-nano blending systems have been devised to equip them with an appropriate aerodynamic character to enable efficient pulmonary aerosolization and inhalation. The late COVID-19 infection is met with acute respiratory distress syndrome and cancer. Chitosan and its derivatives are found useful in combating HCoV and cancer as a function of their molecular weight, substituent type and its degree of substitution. The interest in chitosan is expected to rise in the next decade from the perspectives of drug delivery in combination with its therapeutic performance.

Stealth Coating of Nanoparticles in Drug-Delivery Systems.

Nanoparticles (NPs) have emerged as a powerful drug-delivery tool for cancer therapies to enhance the specificity of drug actions, while reducing the systemic side effects. Nonetheless, NPs interact massively with the surrounding physiological environments including plasma proteins upon administration into the bloodstream. Consequently, they are rapidly cleared from the blood circulation by the mononuclear phagocyte system (MPS) or complement system, resulting in a premature elimination that will cause the drug release at off-target sites. By grafting a stealth coating layer onto the surface of NPs, the blood circulation half-life of nanomaterials can be improved by escaping the recognition and clearance of the immune system. This review focuses on the basic concept underlying the stealth behavior of NPs by polymer coating, whereby the fundamental surface coating characteristics such as molecular weight, surface chain density as well as conformations of polymer chains are of utmost importance for efficient protection of NPs. In addition, the most commonly used stealth polymers such as poly(ethylene glycol) (PEG), poly(2-oxazoline) (POx), and poly(zwitterions) in developing long-circulating NPs for drug delivery are also thoroughly discussed. The biomimetic strategies, including the cell-membrane camouflaging technique and CD47 functionalization for the development of stealth nano-delivery systems, are highlighted in this review as well.

In vivo antitumour properties of tribenzyltin carboxylates in a 4T1 murine metastatic mammary tumour model: Enhanced efficacy by PLGA nanoparticles.

This study reports the in vivo performance of two tribenzyltin carboxylate complexes, tri(4-fluorobenzyl)tin[(N,N-diisopropylcarbamothioyl)sulfanyl]acetate (C1) and tribenzyltin isonicotinate (C9), in their native form as well as in a poly(lactic-co-glycolic acid) (PLGA)-based nanoformulation, to assess their potential to be translated into clinically useful agents. In a 4T1 murine metastatic mammary tumour model, single intravenous administration of C1 (2.7 mg/kg) and C9 (2.1 mg/kg; 2.1 mg/kg C9 is equivalent to 2.7 mg/kg C1) induced greater tumour growth delay than cisplatin and doxorubicin at equivalent doses, while a double-dose regimen demonstrated a much greater tumour growth delay than the single-dose treated groups. To improve the efficacy of the complexes in vivo, C1 and C9 were further integrated into PLGA nanoparticles to yield nanosized PLGA-C1 (183.7 ±â€¯0.8 nm) and PLGA-C9 (163.2 ±â€¯1.2 nm), respectively. Single intravenous administration of PLGA-C1 (2.7 mg C1 equivalent/kg) and PLGA-C9 (2.1 mg C9 equivalent/kg) induced greater tumour growth delay (33% reduction in the area under curve compared to that of free C1 and C9). Multiple-dose administration of PLGA-C1 (5.4 mg C1 equivalent/kg) and PLGA-C9 (4.2 mg C9 equivalent/kg) induced tumour growth suppression at the end of the study (21.7 and 34.6% reduction relative to the size on day 1 for the double-dose regimen; 73.5 and 79.0% reduction relative to the size on day 1 for the triple-dose regimen, respectively). Such tumour growth suppression was not observed in mice receiving multiple-dose regimens of free C1 and C9. Histopathological analysis revealed that metastasis to the lung and liver was inhibited in mice receiving PLGA-C1 and PLGA-C9. The current study has demonstrated the improved in vivo antitumour efficacies of C1 and C9 compared with conventional chemotherapy drugs and the enhancement of the efficacies of these agents via a robust PLGA-based nanoformulation and multiple-drug administration approach.

Report: Cytotoxic activity of phytochemicals from the stem bark of Calophyllum castaneum.

Phytochemical investigation on the dichloromethane stem bark extract of Calophyllum castaneum resulted in the isolation of five compounds, namely isoblancoic acid (1), blancoic acid (2), euxanthone (3), friedelin (4) and friedelinol (5). All these compounds were isolated for the first time from this plant. Their chemical structures were elucidated based on the spectroscopic analyses. The cytotoxicity of compounds 1-5 was assessed on a panel of cancer cell lines including bone (Saos-2, mg63), colorectal (HT29, Caco-2, HCC2998, SW48, HCT116, KM12), liver (HepG2), lung (H1299, Calu-3), and brain (C6), using 5-fluorouracil as positive control. Pronounced antiproliferative activities were observed for compound 1 which exhibited a comparable activity with the positive control, against brain (C6) and colorectal (SW48, KM12, HCT116) cancer cell lines showing IC50 values in the range of 14 to 65µM. Meanwhile, compound 5 displayed a greater cytotoxic effect showing at least 2-fold more strongly than the positive control, against C6 brain cancer cells. The assay findings have unveiled the therapeutic value of phytochemicals from Calophyllum castaneum as anti-cancer agents.

Shielding of Hepatitis B Virus-Like Nanoparticle with Poly(2-Ethyl-2-Oxazoline).

Virus-like nanoparticles (VLNPs) have been studied extensively as nanocarriers for targeted drug delivery to cancer cells. However, VLNPs have intrinsic drawbacks, in particular, potential antigenicity and immunogenicity, which hamper their clinical applications. Thus, they can be eliminated easily and rapidly by host immune systems, rendering these nanoparticles ineffective for drug delivery. The aim of this study was to reduce the antigenicity of hepatitis B core antigen (HBcAg) VLNPs by shielding them with a hydrophilic polymer, poly(2-ethyl-2-oxazoline) (PEtOx). In the present study, an amine-functionalized PEtOx (PEtOx-NH2) was synthesized using the living cationic ring-opening polymerization (CROP) technique and covalently conjugated to HBcAg VLNPs via carboxyl groups. The PEtOx-conjugated HBcAg (PEtOx-HBcAg) VLNPs were characterized with dynamic light scattering and UV-visible spectroscopy. The colloidal stability study indicated that both HBcAg and PEtOx-HBcAg VLNPs maintained their particle size in Tris-buffered saline (TBS) at human body temperature (37 °C) for at least five days. Enzyme-linked immunosorbent assays (ELISA) demonstrated that the antigenicity of PEtOx-HBcAg VLNPs reduced significantly as compared with unconjugated HBcAg VLNPs. This novel conjugation approach provides a general platform for resolving the antigenicity of VLNPs, enabling them to be developed into a variety of nanovehicles for targeted drug delivery.

Solid-liquid extraction of bioactive compounds with antioxidant potential from Alternanthera sesillis (red) and identification of the polyphenols using UHPLC-QqQ-MS/MS.

Alternanthera sessilis (red) (ASR) is an edible herbal plant with many beneficial health effects. This study aimed to investigate the antioxidant components and antioxidant activities of the edible leaves and stems of ASR extracted using solvent of varying polarities namely water, ethanol, ethyl acetate and hexane. ASR leaf extracts showed higher in both antioxidant components and activities than the stem extracts. Among the antioxidant components, the ethanol leaf extract showed higher phenolic (77.29 ±â€¯1.02 mg GAE/g extract) content while the ethyl acetate leaf extract was rich in flavonoids (157.44 ±â€¯10.19 mg RE/g extract), carotenoids (782.97 ±â€¯10.78 mg BE/g extract) and betalains (betanin: 67.08 ±â€¯0.49 mg/g extract; amaranthin: 93.94 ±â€¯0.68 mg/g extract and betaxanthin: 53.92 ±â€¯0.88 mg/g extract). Nevertheless, the ethanol leaf extract showed the highest DPPH radical scavenging activity and ABTS radical cation scavenging activity. It also exhibited highest ferric reducing activity among all the extracts. Four polyphenolic compounds from ASR leaf, namely ferulic acid, rutin, quercetin and apigenin, were identified and quantified using ultra high performance liquid chromatography. The existence of these compounds was further verified using tandem mass spectrometry. These current results indicate that ASR leaf particularly the ethanol extract has the potential to be exploited as a source of natural antioxidants.

In vitro functional evaluation of isolaureline, dicentrine and glaucine enantiomers at 5-HT2 and α1 receptors.

Compounds with activity at serotonin (5-hydroxytryptamine) 5-HT2 and α1 adrenergic receptors have potential for the treatment of central nervous system disorders, drug addiction or overdose. Isolaureline, dicentrine and glaucine enantiomers were synthesized, and their in vitro functional activities at human 5-HT2 and adrenergic α1 receptor subtypes were evaluated. The enantiomers of isolaureline and dicentrine acted as antagonists at 5-HT2 and α1 receptors with (R)-isolaureline showing the greatest potency (pKb  = 8.14 at the 5-HT2C receptor). Both (R)- and (S)-glaucine also antagonized α1 receptors, but they behaved very differently to the other compounds at 5-HT2 receptors: (S)-glaucine acted as a partial agonist at all three 5-HT2 receptor subtypes, whereas (R)-glaucine appeared to act as a positive allosteric modulator at the 5-HT2A receptor.

Lung cancer: active therapeutic targeting and inhalational nanoproduct design.

INTRODUCTION: Pulmonary drug delivery is organ-specific and benefits local drug action for lung cancer. The use of nanotechnology and targeting ligand enables cellular-specific drug action. Combination approaches increase therapeutic efficacy and reduce adverse effects of cancer chemotherapeutics that have narrow therapeutic index window and high cytotoxicity levels. The current progress of inhaled cancer chemotherapeutics has not been examined with respect to targeting strategy and clinical application potential. AREAS COVERED: This review examines the state of the art in passive (processing and formulation) and active (targeting ligand and receptor binding) technologies in association with the use of nanocarrier to combat lung cancer. It highlights routes to equip nanocarrier with targeting ligands as a function of the chemistry of participating biomolecules and challenges in inhalational nanoproduct development and clinical applications. Both research and review articles were examined using the Scopus, Elsevier, Web of Science, Chemical Abstracts, Medline, CASREACT, CHEMCATS, and CHEMLIST database with the majority of information retrieved between those of 2000-2018. EXPERT COMMENTARY: The therapeutic efficacy of targeting ligand-decorated nanocarriers needs to be demonstrated in vivo in the form of finished inhalational products. Their inhalation efficiency and medical responses require further examination. Clinical application of inhaled nanocancer chemotherapeutics is premature.

Correction: Synthesis and evaluation of nuciferine and roemerine enantiomers as 5-HT2 and α1 receptor antagonists.

[This corrects the article DOI: 10.1039/C7MD00629B.].

Synthesis and evaluation of nuciferine and roemerine enantiomers as 5-HT2 and α1 receptor antagonists.

In this study, the (S)-enantiomers of the aporphine alkaloids, nuciferine and roemerine, were prepared via a synthetic route involving catalytic asymmetric hydrogenation and both stereoisomers were evaluated in vitro for functional activity at human 5-HT2 and adrenergic α1 receptor subtypes using a transforming growth factor-α shedding assay. Both enantiomers of each of the compounds were found to act as antagonists at 5-HT2 and α1 receptors. (R)-roemerine was the most potent compound at 5-HT2A and 5-HT2C receptors (pKb = 7.8-7.9) with good selectivity compared to (S)-roemerine at these two receptors and compared to its activity at 5-HT2B, α1A, α1B and α1D receptors.

Suppression of Staphylococcus aureus biofilm formation and virulence by a benzimidazole derivative, UM-C162.

Staphylococcus aureus is a major cause of nosocomial infections and secretes a diverse spectrum of virulence determinants as well as forms biofilm. The emergence of antibiotic-resistant S. aureus highlights the need for alternative forms of therapeutics other than conventional antibiotics. One route to meet this need is screening small molecule derivatives for potential anti-infective activity. Using a previously optimized C. elegans - S. aureus small molecule screen, we identified a benzimidazole derivative, UM-C162, which rescued nematodes from a S. aureus infection. UM-C162 prevented the formation of biofilm in a dose-dependent manner without interfering with bacterial viability. To examine the effect of UM-C162 on the expression of S. aureus virulence genes, a genome-wide transcriptome analysis was performed on UM-C162-treated pathogen. Our data indicated that the genes associated with biofilm formation, particularly those involved in bacterial attachment, were suppressed in UM-C162-treated bacteria. Additionally, a set of genes encoding vital S. aureus virulence factors were also down-regulated in the presence of UM-C162. Further biochemical analysis validated that UM-C162-mediated disruption of S. aureus hemolysins, proteases and clumping factors production. Collectively, our findings propose that UM-C162 is a promising compound that can be further developed as an anti-virulence agent to control S. aureus infections.