Butein inhibits oral squamous cell carcinoma growth via promoting MCL-1 ubiquitination.

Oral squamous cell carcinoma (OSCC) is the most common malignant head and neck carcinoma type. Myeloid cell leukemia-1 (MCL-1), an anti-apoptotic BCL-1 protein, has been verified to be among the most highly upregulated pathologic proteins in human cancers linked to tumor relapse, poor prognosis and therapeutic resistance. Herein, therapeutic targeting MCL-1 is an attractive focus for cancer treatment. The present study found that butein, a potential phytochemical compound, exerted profound antitumor effects on OSCC cells. Butein treatment significantly inhibited cell viability, proliferation capacity and colony formation ability, and activated cell apoptotic process. Further potential mechanism investigation showed that promoting MCL-1 ubiquitination and degradation is the major reason for butein-mediated OSCC cell cytotoxicity. Our results uncovered that butein could facilitate E3 ligase FBW7 combined with MCL-1, which contributed to an increase in the ubiquitination of MCL-1 Ub-K48 and degradation. The results of both in vitro cell experiments and in vivo xenograft models imply a critical antitumor function of butein with the well-tolerated feature, and it might be an attractive and promising agent for OSCC treatment.

Inhibition of macrophage MAPK/NF-κB pathway and Th2 axis by mangiferin ameliorates MC903-induced atopic dermatitis.

Available online Atopic dermatitis (AD) is a chronic, persistent inflammatory skin disease characterized by eczema-like lesions and itching. Although topical steroids have been reported for treating AD, they are associated with adverse effects. Thus, safer medications are needed for those who cannot tolerate these agents for long periods. Mangiferin (MAN) is a flavonoid widely found in many herbs, with significant anti-inflammatory and immunomodulatory activities. However, the potential modulatory effects and mechanisms of MAN in treating Th2 inflammation in AD are unknown. In the present study, we reported that MAN could reduce inflammatory cell infiltration and scratching at the lesion site by decreasing MC903-induced levels of Th2-type cytokines, Histamine, thymic stromal lymphopoietin, Leukotriene B4, and immunoglobulin E. The mechanism may be related to reductions in MAPK and NF-κB-associated protein phosphorylation by macrophages. The results suggested that MAN may be a promising therapeutic agent for AD.

Antifungal activity of ruthenium (II) complex combined with fluconazole against drug-resistant Candida albicans in vitro and its anti-invasive infection in vivo.

With the abuse of antibiotics and azoles, drug-resistant Candida albicans infections have increased sharply and are spreading rapidly, thereby significantly reducing the antifungal efficacy of existing therapeutics. Several patients die of fungal infections every year. Therefore, there is an urgent requirement to develop new drugs. Accordingly, we synthesized a series of polypyridyl ruthenium (II) complexes having the formula [Ru (NN)2 (bpm)] (PF6)2 (N-N = 2,2'-bipyridine) (bpy, in Ru1), 1,10-phenanthroline (phen, in Ru2), 4,7-diphenyl-1,10-phenanthroline (DIP, in Ru3) (bpm = 2,2'-bipyrimidine) and studied their antifungal activities. Ru3 alone had no effect on the drug-resistant strains, but Ru3 combined with fluconazole (FLC) exhibited significant antifungal activity on drug-resistant strains. A high-dose combination of Ru3 and FLC exhibited direct fungicidal activity by promoting the accumulation of reactive oxygen species and damaging the cellular structure of C. albicans. Additionally, the combination of Ru3 and FLC demonstrated potent antifungal efficacy in vivo in a mouse model of invasive candidiasis. Moreover, the combination significantly improved the survival state of mice, restored their immune systems, and reduced renal injury. These findings could provide ideas for the development of ruthenium (II) complexes as novel antifungal agents for drug-resistant microbial stains.

Dioscin inhibits non-small cell lung cancer cells and activates apoptosis by downregulation of Survivin.

Human malignancies exhibit elevated levels of survivin, and have been linked to poor prognosis. Targeting survivin expression is a promising therapeutic strategy against cancer cells. Natural compounds have become a hot topic in research due to their non-toxic, non-invasive, and efficient treatment of multiple diseases. In this current investigation, it was discovered that Dioscin, as a natural compound, exerted profound antitumor activity against NSCLC cell lines, inhibiting NSCLC cell viability and promoting apoptosis. Further mechanistic studies showed that Dioscin promoted ubiquitination-mediated survivin degradation via strengthening the interaction between survivin and the E3 ubiquitin ligase Fbxl7. Furthermore, Dioscin exhibited a strong tumor suppressive effect in xenograft tumor models, and Dioscin treatment led to a notable decrease in tumor volume and weight. Based on our findings, Dioscin is expected to be a potential antitumor agent for non-small cell lung cancer treatment.

TRAF4 regulates ubiquitination-modulated survivin turnover and confers radioresistance.

Nasopharyngeal carcinoma (NPC) is the most common cancer originating in the nasopharynx. Despite continuous improvement in treatment strategies, recurrence or persistence of cancer after radiotherapy is still inevitable, highlighting the need to identify therapeutic resistance factors and develop effective methods for NPC treatment. Herein, we found that TRAF4 is overexpressed in NPC cells and tissues. Knockdown TRAF4 significantly increased the radiosensitivity of NPC cells, possibly by inhibiting the Akt/Wee1/CDK1 axis, thereby suppressing survivin phosphorylation and promoting its degradation by FBXL7. TRAF4 is positively correlated with p-Akt and survivin in NPC tissues. High protein levels of TRAF4 were observed in acquired radioresistant NPC cells, and knockdown of TRAF4 overcomes radioresistant in vitro and the xenograft mouse model. Altogether, our study highlights the TRAF4-survivin axis as a potential therapeutic target for radiosensitization in NPC.

Exploration of costunolide derivatives as potential anti-inflammatory agents for topical treatment of atopic dermatitis by inhibiting MAPK/NF-κB pathways.

Atopic dermatitis (AD) is a common inflammatory disease and it is very difficult to treat. In the present work, a series of costunolide derivatives have been prepared, and in vitro and in vivo anti-inflammatory activities have evaluated. The results showed that most derivatives displayed good inhibition of NO generation with low cytotoxicity, and 7d could inhibit the phosphorylation of P38, P65 NF-κB and IκB-α in LPS-induced RAW264.7 model. The in vivo researches showed that 7d could improve skin injury symptoms, decrease Th2-type cytokine levels, inhibit HIS levels, alleviate scratching and repaire the damaged skin barrier through the inhibition of phosphorylation of MAPK and NF-κB signaling pathways on MC903-induced AD model. Therefore, costunolide derivatives may be new potent anti-AD agents for further study.

Isoliquiritigenin Inhibits Oral Squamous Cell Carcinoma and Overcomes Chemoresistance by Destruction of Survivin.

The oncoprotein survivin plays a pivotal role in controlling cell division and preventing apoptosis by inhibiting caspase activation. Its significant contribution to tumorigenesis and therapeutic resistance has been well established. Isoliquiritigenin (ISL), a natural compound, has been recognized for its powerful inhibitory effects against various tumors. However, whether ISL exerts regulatory effects on survivin and its underlying mechanism in oral squamous cell carcinoma (OSCC) remains unclear. Here, we found that ISL inhibited the viability and colony formation of OSCC, and promoted their apoptosis. The immunoblotting data showed that ISL treatment significantly decreased survivin expression. Mechanistically, ISL suppressed survivin phosphorylation on Thr34 by deregulating Akt-Wee1-CDK1 signaling, which facilitated survivin for ubiquitination degradation. ISL inhibited CAL27 tumor growth and decreased p-Akt and survivin expression in vivo. Meanwhile, survivin overexpression caused cisplatin resistance of OSCC cells. ISL alone or combined with cisplatin overcame chemoresistance in OSCC cells. Overall, our results revealed that ISL exerted potent inhibitory effects via inducing Akt-dependent survivin ubiquitination in OSCC cells.

Gastrodin overcomes chemoresistance via inhibiting Skp2-mediated glycolysis.

Aerobic glycolysis, a typical phenotype in human tumors, is associated with tumor progression and chemotherapy resistance. The present study demonstrated that cisplatin-resistant oral squamous cell carcinoma (OSCC) cells exerted a stronger glycolysis ability, which was associated with hexokinase 2 (HK2) overexpression. Additionally, the tumor growth of OSCC cells was delayed in vivo and the glycolysis was notably decreased following HK2 knockdown. The natural compound screening revealed that gastrodin could be an effective candidate for OSCC therapy since it inhibited HK2-mediated glucose metabolism and promoted endogenous OSCC cell apoptosis. Furthermore, gastrodin could bind to protein kinase B (Akt) and suppress its activity, thus downregulating HK2 at the transcriptional level. Additionally, S-phase kinase-associated protein 2 (Skp2) was highly expressed in OSCC cells, while K63-linked ubiquitination of Akt was inhibited in Skp2-depleted cisplatin-resistant OSCC cells. Gastrodin could also inhibit the cisplatin resistance of OSCC cells in vivo, particularly when combined with the Skp2 inhibitor, SZL P1-41. Overall, the aforementioned finding suggested that targeting the Skp2-Akt axis could be a potential therapeutic strategy for treating OSCC and overcoming chemoresistance.

Super-Low Friction Electrification Achieved on Polytetrafluoroethylene Films-Based Triboelectric Nanogenerators Lubricated by Graphene-Doped Silicone Oil.

The novel proposal of Wang's triboelectric nanogenerator (TENG) has inspired extensive efforts to explore energy harvesting devices from the living environment for the upcoming low-carbon society. The inevitable friction and wear problems of the tribolayer materials become one of the biggest obstacles for attaining high-performance TENGs. To achieve super-low friction electrification of the TENGs, the tribological and electrical behaviors of the sliding-mode TENGs based on polytetrafluoroethylene (PTFE) films and metallic balls under both dry friction and liquid lubrication conditions were investigated by using a customized testing platform with a ball-on-flat configuration. Most interestingly, a super-low friction coefficient of 0.008 was achieved under graphene-doped silicone oil lubrication. The corresponding wear rate of the PTFE film was drastically decreased to 8.19 × 10-5 mm3/Nm. Simultaneously, the output short-circuit current and open-circuit voltage were enhanced by 6.8 times and 3.0 times, respectively, compared to the dry friction condition. The outstanding triboelectrical performances of the PTFE film when sliding against a steel ball are attributed to the synergistic lubricating effects of the silicone oil and the graphene nanosheets. The current research provides valuable insights into achieving the macro-scale superlubricity of the TENGs in practical industrial applications.

Tanshinone IIA inhibits cell viability and promotes PUMA-mediated apoptosis of oral squamous cell carcinoma.

Apoptosis alteration is responsible for tumorigenesis and tumor resistance to therapies. The natural product Tanshinone IIA (Tan IIA) exhibits potent inhibitory effects against various tumors. However, the effect of Tan IIA on apoptosis and its underlying mechanism remains elusive in oral squamous cell carcinoma (OSCC). Here, we demonstrated that Tan IIA dose-dependently suppressed cell viability and colony formation in CAL27, SCC4, and SCC25 cells. Moreover, Tan IIA inhibited Akt activation from inducing Foxo3a dephosphorylation and PUMA-mediated apoptosis. PUMA or Foxo3a knockdown compromised the inhibitory effect of Tan IIA on OSCC cells. Tan IIA administration inhibited CAL27-deprived xenograft tumor growth and increased PUMA expression in vivo. Tan IIA synergistically intensified the efficacy of CDDP/5-FU-based chemotherapy on OSCC cells. Overall, our results revealed that Tan IIA exerted potent antitumor effects via promoting PUMA-mediated apoptosis in OSCC cells.

Cyclometalated iridium(III) complexes combined with fluconazole: antifungal activity against resistant C. albicans.

Candida albicans (C. albicans) is a ubiquitous clinical fungal pathogen. In recent years, combination therapy, a potential treatment method to overcome C. albicans resistance, has gained traction. In this study, we synthesized a series of cyclometalated iridium(III) complexes with the formula [Ir(C-N)2(tpphz)](PF6) (C-N = 2-phenylpyridine (ppy, in Ir1), 2-(2-thienyl)pyridine (thpy, in Ir2), 2-(2,4-difluorophenyl) pyridine (dfppy, in Ir3), tpphz = tetrapyrido[3,2-a:2',3'-c:3'',2''-h:2''',3'''-j]phenazine) and polypyridyl ruthenium(II) complexes with the formula [Ru(N-N)2(tpphz)](PF6)2 (N-N = 2,2'-bipyridine (bpy, in Ru1), 1,10-phenanthroline (phen, in Ru2), 4,7-diphenyl-1,10-phenanthroline (DIP, in Ru3)), and investigated their antifungal activities against drug-resistant C. albicans and their combination with fluconazole (FLC). Of which, the combination of the lead iridium(III) complex Ir2 and FLC showed strong antifungal activity against drug-resistant C. albicans. Mechanism studies have shown that they can inhibit the formation of hyphae and biofilm, damage mitochondrial function and accumulate intracellular ROS. Therefore, iridium(III) complexes combined with FLC can be used as a promising treatment to exert anti-drug-resistant C. albicans activity, in order to improve the treatment efficiency of fungal infection.

Survivin degradation by bergenin overcomes pemetrexed resistance.

PURPOSE: Chemoresistance is a primary factor for treatment failure and tumor recurrence in non-small cell lung cancer (NSCLC) patients. The oncoprotein survivin is commonly upregulated in human malignancies and is associated with poor prognosis, but its effect on carcinogenesis and chemoresistance in NSCLC is not yet evident, and to explore an effective inhibitor targeting survivin expression is urgently needed. METHODS: The protumor characteristics of survivin and antitumor activities of bergenin in NSCLC cells were examined by MTS, colony formation assays, immunoblot, immunohistochemistry, and in vivo xenograft development. RESULTS: Survivin was upregulated in non-small cell lung cancer (NSCLC) tissues, while its depletion inhibited NSCLC tumorigenesis. The current study focused on bergenin, identifying its effective antitumor effect on NSCLC cells both in vivo and in vitro. The results showed that bergenin could inhibit cell proliferation and induce the intrinsic pathway of apoptosis via downregulating survivin. Mechanistically, bergenin reduced the phosphorylation of survivin via inhibiting the Akt/Wee1/CDK1 signaling pathway, thus resulting in enhanced interaction between survivin and E3 ligase Fbxl7 to promote survivin ubiquitination and degradation. Furthermore, bergenin promoted chemoresistance in NSCLC cells re-sensitized to pemetrexed treatment. CONCLUSIONS: Survivin overexpression is required for maintaining multiple malignant phenotypes of NSCLC cells. Bergenin exerts a potent antitumor effect on NSCLC via targeting survivin, rendering it a promising agent for the treatment of NSCLC.

Cadmium accumulation and isotope fractionation in typical protozoa Tetrahymena: A new perspective on remediation of Cd pollution in wastewater.

Cadmium (Cd) pollution threatens water safety and human health, which has raised serious public concern. Tetrahymena is a model protozoan, possessing the potential to remediate Cd contaminated water given the rapid expression of thiols. However, the mechanism of Cd accumulation in Tetrahymena has not been well understood, which hinders its application in environmental remediation. This study elucidated the pathway of Cd accumulation in Tetrahymena using Cd isotope fractionation. Our results showed that Tetrahymena preferentially absorb light Cd isotopes, with Δ114/110CdTetrahymena-solution = -0.20 ± 0.02‰ ∼ - 0.29 ± 0.02‰, which implies that the intracellular Cd is probably in the form of Cd-S. The fractionation generated by Cd complexation with thiols is constant (Δ114/110CdTetrahymena-remaining solution ∼ -0.28 ± 0.02‰), which is not affected by the concentrations of Cd in intracellular and culture medium, nor by the physiological changes in cells. Furthermore, the detoxification process of Tetrahymena results in an increase in cellular Cd accumulation from 11.7% to 23.3% with the elevated Cd concentrations in batch Cd stress culture experiments. This study highlights the promising application of Cd isotope fractionation in Tetrahymena for the remediation of heavy metal pollution in water.

Thalidomide promotes NLRP3/caspase-1-mediated pyroptosis of macrophages in Talaromyces marneffei infection.

Macrophage-derived inflammatory cytokines are critical for host defense against Talaromyces marneffei (T. marneffei) infection among HIV/AIDS patients, and excessive inflammatory cytokines are associated with poor outcomes of AIDS-associated talaromycosis. However, the underlying mechanisms of macrophage-caused pyroptosis and cytokine storm are poorly understood. Here, in the T. marneffei-infected mice and macrophages, we show that T. marneffei induced pyroptosis in macrophages through the NLRP3/caspase-1 pathway. The immunomodulatory drug thalidomide could promote the pyroptosis of macrophages infected T. marneffei. In T. marneffei-infected mice, the splenic macrophages underwent increasing pyroptosis as talaromycosis deteriorated. Thalidomide ameliorated inflammation of mice, while amphotericin B (AmB) in combination with thalidomide did not improve overall survival compared with AmB alone. Taken together, our findings suggest that thalidomide promotes NLRP3/caspase-1-mediated pyroptosis of macrophages in T. marneffei infection.

IFNγ blockade in capillary leak site improves tumour chemotherapy by inhibiting lactate-induced endocytosis of vascular endothelial-cadherins.

IFNγ has long been recognised as a key mediator of tumour immunity and angiostasis. However, IFNγ modulation for cancer therapy is still unsuccessful due to its complex effects on various host cells. In this study, we found that treatment of Lewis lung carcinoma transplants with cisplatin often caused IFNγ-dependent tumour vascular damage. IFNγ induced endothelial glycolysis and lactate production, leading to enhanced endocytosis of vascular endothelial (VE)-cadherin and vessel leakage. We have also developed anti-IFNγ nanoparticles coated with a clot-binding peptide CREKA (CREKA-lipo-anti-IFNγ), which targets the fibrin-fibronectin complex that appears in the leaky site of damaged tumour blood vessels. Blocking IFNγ activity in the leakage site of capillaries using nanoparticles rescued VE-cadherin distribution on the endothelial cellular surface, promoted blood vessel integrity, and improved drug delivery. In conclusion, IFNγ blockade in capillary leak site protected tumour blood vessels from lactate-dependent VE-cadherin loss and enhanced drug delivery during chemotherapy, which provides a basis for tissue-specific IFNγ blockade for tumour therapy.

Polyphyllin I Effects Candida albicans via Inhibition of Virulence Factors.

Paris polyphylla is often used in Chinese medicine to treat conditions such as carbuncles, trauma, snake bites, and mosquito bites. In the present study, we investigated the effect and mechanism of the morphological transition and extracellular phospholipase activity of Candida albicans treated with polyphyllin I (PPI). First, the minimum inhibitory concentration and antifungal activity of PPI were evaluated using the multiple microdilution method and time-killing assays. Then, the effect of PPI on the morphological transition of Candida albicans in Spider liquid medium and Sabouraud-dextrose liquid medium containing 10% fetal bovine serum was observed under an inverted microscope and by scanning electron microscopy. Finally, egg yolk agar plates were used to evaluate extracellular phospholipase activity. Gene expression was detected by real-time quantitative polymerase chain reaction analysis. Our results suggest that PPI inhibited the transition from the yeast to the hyphal stage and decreased secreted aspartyl proteinase activity. We further confirmed that PPI significantly downregulated the expression of extracellular phospholipase genes and cAMP-PKA signaling pathway-related genes. Taken together, our results suggest that PPI exerts anti-Candida albicans activity by inhibiting virulence characteristics, including the yeast-to-hyphal transition and the secretion of aspartyl proteases and phospholipases. The study results also indicated that PPI could be a promising therapeutic strategy for Candida albicans.

Reactive oxygen metabolism in the proliferation of Korean pine embryogenic callus cells promoted by exogenous GSH.

Exogenous glutathione (GSH) promotes the proliferation of embryogenic callus (EC) cells in Korean pine in the course of somatic embryogenesis, and reactive oxygen species (ROS) may play an important role in regulating the proliferation of EC cells by exogenous GSH. However, the concrete metabolic response of ROS is unclear. In this study, two cell lines of Korean pine with high proliferative potential 001#-001 (F, Fast proliferative potential cell line is abbreviated as F) and low proliferative potential 001#-010 (S, Slow proliferative potential cell line is abbreviated as S) were used as test materials. The responses of ROS-related enzymes and substances to exogenous GSH and L-Buthionine-sulfoximine (BSO) were investigated in EC cells. The results showed that the exogenous addition of GSH increased the number of early somatic embryogenesis (SEs) in EC cells of both F and S cell lines, decreased the amount of cell death in both cell lines. Exogenous addition of GSH promoted cell division in both cell lines, increased intracellular superoxide dismutase (SOD) and catalase (CAT) activities, inhibited intracellular hydrogen peroxide (H2O2), malondialdehyde (MDA) and nitric oxide (NO) production, and increased NO/ROS ratio. In conclusion, the exogenous GSH promoting the proliferation of Korean pine EC cells, the activity of intracellular antioxidant enzymes was enhanced, the ROS level was reduced, and the resistance of cells to stress was enhanced.

Integration of metabolomics and transcriptomics analyses reveals sphingosine-1-phosphate-mediated S1PR2/PI3K/Akt pathway involved in Talaromyces marneffei infection of macrophages.

Talaromycosis is a fatal mycosis caused by the thermally dimorphic fungus Talaromyces marneffei (T. marneffei). The pathogenic mechanisms of talaromycosis are still poorly understood. This work combined metabolomics, transcriptomics, and verification experiments in vivo and in vitro to detect metabolic profiles and differentially expressed genes (DEGs) in T. marneffei infected and uninfected macrophages to explore possible pathogenesis and underlying mechanisms. A total of 256 differential metabolites (117 up-regulated and 148 down-regulated) and 1320 DEGs (1286 up-regulated and 34 down-regulated) were identified between the two groups. Integrative metabolomics and transcriptomics analysis showed sphingolipid signaling pathway is the most influential. Verification experiments showed that compared with the control group, the production of sphingosine-1-phosphate (S1P) and the expression of the S1PR1, S1PR2, phosphor-PI3K, and phosphor-Akt genes involved in the sphingolipid signaling pathway have significantly increased in the T. marneffei infection group (p < 0.05). T. marneffei activates the S1PR2/PI3K/Akt pathways in J774A.1 macrophage, regulation of the S1P singling might serve as a promising therapeutic strategy for talaromycosis.

Heterogeneous Fenton oxidation of 2,4-dichlorophenol catalyzed by PEGylated nanoscale zero-valent iron supported by biochar.

The excessive use of herbicides and fungicides containing 2,4-dichlorophenol (2,4-DCP) has led to serious environmental water pollution; 2,4-DCP is chemically stable and difficult to be degraded effectively by biological and physical methods. And the degradation of 2,4-DCP using advanced oxidation techniques has been a hot topic. Biochar, polyethylene glycol, ferrous sulfate, and sodium borohydride were used to synthesize the heterogeneous catalyst PEGylated nanoscale zero-valent iron supported by biochar (PEG-nZVI@BC). The catalyst was characterized using scanning electron microscope (SEM) and other means to determine its physicochemical properties. Catalytic performance and mechanism of this catalyst with hydrogen peroxide for the oxidation of 2,4-DCP were investigated. The results showed that PEG-nZVI@BC had good dispersibility, stability, and inoxidizability; the degradation efficiency of 50 mg/L 2,4-DCP by PEG-nZVI@BC/H2O2 system 92.94%, 1.68 times higher than that of nZVI/H2O2 system; there are both free radical and non-free radical pathways in PEG-nZVI@BC/H2O2 system; the degradation process of 2,4-DCP includes hydroxylation, dechlorination, and ring-opening. Overall, PEG-nZVI@BC is a promising heterogeneous catalyst for the degradation of 2,4-DCP.

New tocopherol and acylphloroglucinol derivatives from Dryopteris crassirhizoma and their antimicrobial activities.

Nine previously undescribed compounds including six tocopherol derivatives (1-6) and three acylphloroglucinol derivatives (7-9) were isolated and characterized from the plants of Dryopteris crassirhizoma. Their structures with absolute configurations were determined by extensive spectroscopic analyses, including IR, HRESIMS, NMR, and calculated electronic circular dichroism (ECD). Compounds 1 and 2 are the first tocopheroid derivatives possessing unique 2,5-dimethylcyclopent-4-ene-1,3-dione carbon skeleton, and compounds 3-6 were new 5a-norcyclopentenones having a spirofused bicyclic carbon skeleton. The biosynthetic pathway of compounds 1-6 was postulated. When combined with fluconazole (FLC), compound 3 showed significant antifungal activity against standard Candida albicans with MIC50 value of 1.19 µg/mL (FLC: 3.41 µg/mL). Furthermore, the anti-plant pathogenic fungi and bacterial activities have been evaluated in vitro, compounds 5 and 8 showed anti-Verticillium dahlia and Sclerotinia sclerotiorum with MIC value of 50 µg/mL, respectively. Compounds 1 and 5 exhibited moderate antibacterial activities against Micrococcus luteus with MIC value of 50 µg/mL, respectively.