anti-MRSA Activity Research Articles

Hypericin and Pheophorbide a Mediated Photodynamic Therapy Fighting MRSA Wound Infections: A Translational Study from In Vitro to In Vivo.

High prevalence rates of methicillin-resistant Staphylococcus aureus (MRSA) and lack of effective antibacterial treatments urge discovery of alternative therapeutic modalities. The advent of antibacterial photodynamic therapy (aPDT) is a promising alternative, composing rapid, nonselective cell destruction without generating resistance. We used a panel of clinically relevant MRSA to evaluate hypericin (Hy) and pheophobide a (Pa)-mediated PDT with clinically approved methylene blue (MB). We translated the promising in vitro anti-MRSA activity of selected compounds to a full-thick MRSA wound infection model in mice (in vivo) and the interaction of aPDT innate immune system (cytotoxicity towards neutrophils). Hy-PDT consistently displayed lower minimum bactericidal concentration (MBC) values (0.625–10 µM) against ATCC RN4220/pUL5054 and a whole panel of community-associated (CA)-MRSA compared to Pa or MB. Interestingly, Pa-PDT and Hy-PDT topical application demonstrated encouraging in vivo anti-MRSA activity (>1 log10 CFU reduction). Furthermore, histological analysis showed wound healing via re-epithelization was best in the Hy-PDT group. Importantly, the dark toxicity of Hy was significantly lower (p < 0.05) on neutrophils compared to Pa or MB. Overall, Hy-mediated PDT is a promising alternative to treat MRSA wound infections, and further rigorous mechanistic studies are warranted.

Genomic Insights into the Antimicrobial and Anticancer Potential of Streptomyces sp. A1-08 Isolated from Volcanic Soils of Mount Mayon, Philippines

Antimicrobial resistance (AMR) poses a global and developmental threat to humanity. The rapid emergence and spread of drug-resistant pathogens resulted in the ineffective use of currently available antibiotics. Therefore, there is a need to continue searching for additional sources of antibiotics, such as actinomycetes, which can potentially harbor unique and effective secondary metabolites. Furthermore, it is interesting to consider poorly explored environments like volcanoes, which can be potential sources of drug leads for medically important natural products. This study reports the antimicrobial activity of actinomycetes isolated from volcanic soil samples collected from Mount Mayon, Albay, Philippines. A total of 13 out of 30 morphologically distinct actinomycete isolates showed antagonistic activity against test microorganisms. Isolate A1-08, the focus of the study, exhibited a wide spectrum of antimicrobial activity against Salmonella enterica, Klebsiella pneumoniae, Staphylococcus aureus, methicillin-resistant S. aureus(MRSA), Candida albicans, Aspergillus niger, and Fusarium sp. Moreover, A1-08 was found to have anti-methicillin resistant S. aureus (MIC = 2.50 mg/mL) and anticancer activity against human colorectal cancer (HCT116) cell line (IC50 = 21.54 μg/mL). Whole-genome sequence-based phylogenetic analysis supported a novel species of Streptomyces closely related to S. olivaceus NRRL B-3009. A total of 48 biosynthetic gene clusters (BGCs) were identified that may be responsible for the biosynthesis of known and potentially novel secondary metabolites. This study concludes that Streptomyces sp. A1-08, a potentially novel species, is a good candidate to produce broad-spectrum antibiotics with anti-MRSA and anti-cancer activities and possibly novel secondary bioactive metabolites of medical and pharmaceutical importance.

Streptomyces poriferorum sp. nov., a novel marine sponge-derived Actinobacteria species expressing anti-MRSA activity

Marine sponges represent a rich source of uncharacterized microbial diversity, and many are host to microorganisms that produce biologically active specialized metabolites. Here, a polyphasic approach was used to characterize two Actinobacteria strains, P01-B04T and P01-F02, that were isolated from the marine sponges Geodia barretti (Bowerbank, 1858) and Antho dichotoma (Esper, 1794), respectively. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strains P01-B04T and P01-F02 are closely related to Streptomyces beijiangensis DSM 41794T, Streptomyces laculatispora NRRL B-24909T, and Streptomyces brevispora NRRL B-24910T. The two strains showed nearly identical 16S rRNA gene sequences (99.93%), and the average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) relatedness values were 99.96% and 99.6%, respectively, suggesting that these strains are affiliated with the same species. Chemotaxonomic and culture characteristics of both strains were also consistent with the genus Streptomyces, while phenotypic properties, genome-based comparisons, and phylogenomic analyses distinguished strains P01-B04T and P01-F02 from their closest phylogenetic relatives. In silico analysis predicted that the 8.9 Mb genome of P01-B04T contains at least 41 biosynthetic gene clusters (BGCs) encoding secondary metabolites, indicating that this strain could express diverse bioactive metabolites; in support of this prediction, this strain expressed antibacterial activity against Gram-positive bacteria including a clinical isolate of methicillin-resistant Staphylococcus aureus (MRSA) EAMC30. Based on these results, the marine sponge-associated isolates represent a novel species of the genus Streptomyces, for which the name Streptomyces poriferorum sp. nov. is proposed, with P01-B04T (=DSM 111306T = CCM 9048T) as the type strain.

Three new anthraquinones from the twigs of Cassia auriculata Linn. and their antibacterial activity

Three new anthraquinones ( 1 – 3 ), together with four known analogues ( 4 – 7 ) were isolated from the twigs of Cassia auriculata Linn.. Their structures were elucidated by extensive spectroscopic analysis and comparison of spectroscopic data with those reported in literatures. All compounds were tested for their anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) activity. Compounds 1 , 2 and 7 showed modest antibacterial activity against MRSA with MIC values of 4.2, 5.0, 4.7 μ g/mL, and compounds 3 , 4 , 5 and 6 showed weak antibacterial activity against MRSA with MIC valves of 9.2, 7.6, 7.1, 9.6 μ g/mL, respectively.

Effect of Culture Medium Incorporated with Ocimum sanctum Extract in Enhancing Anti-MRSA activity of Endophytic Fungus, Lasiodiplodia pseudotheobromae

The effect of incorporating plant extract in the culture medium on anti-MRSA activity of Lasiodiplodia pseudotheobromae IBRL OS-64, was investigated in the present study. On disk diffusion assay, the ethyl acetate fungal extract from culture medium supplemented with host plant extract (HPE) of Ocimum sanctum leaves demonstrated good anti-MRSA activity with a diameter inhibition zone of 22.6±0.6 mm. Meanwhile, the minimal inhibition concentration (MIC) values of the extract from YES broth and YES broth incorporated with HPE were 1000 µg/mL and 250 µg/mL, respectively. The MBC values were 8000 µg/mL and 500 µg/mL, respectively. The YES + HPE extracts exerted bactericidal effect against the test bacteria since the MBC/MIC ratio was less than or equal to 4. The time-kill study revealed a 90% of growth reduction of MRSA ATCC 33591 after 16 h exposure to the fungal extract cultured in YES + HPE. Ironically, for fungal extract grown in YES broth, time-kill curve showed a regrowth pattern of bacterial cells after 24 h exposed to the extract. Therefore, the present study suggested that the addition of HPE in the culture medium could enhance the anti-MRSA activity of endophytic fungus, L. pseudotheobromae IBRL OS-64 against MRSA ATCC 33591.

Insights into the molecular properties underlying antibacterial activity of prenylated (iso)flavonoids against MRSA

High resistance towards traditional antibiotics has urged the development of new, natural therapeutics against methicillin-resistant Staphylococcus aureus (MRSA). Prenylated (iso)flavonoids, present mainly in the Fabaceae, can serve as promising candidates. Herein, the anti-MRSA properties of 23 prenylated (iso)flavonoids were assessed in-vitro. The di-prenylated (iso)flavonoids, glabrol (flavanone) and 6,8-diprenyl genistein (isoflavone), together with the mono-prenylated, 4′-O-methyl glabridin (isoflavan), were the most active anti-MRSA compounds (Minimum Inhibitory Concentrations (MIC) ≤ 10 µg/mL, 30 µM). The in-house activity data was complemented with literature data to yield an extended, curated dataset of 67 molecules for the development of robust in-silico prediction models. A QSAR model having a good fit (R2adj 0.61), low average prediction errors and a good predictive power (Q2) for the training (4% and Q2LOO 0.57, respectively) and the test set (5% and Q2test 0.75, respectively) was obtained. Furthermore, the model predicted well the activity of an external validation set (on average 5% prediction errors), as well as the level of activity (low, moderate, high) of prenylated (iso)flavonoids against other Gram-positive bacteria. For the first time, the importance of formal charge, besides hydrophobic volume and hydrogen-bonding, in the anti-MRSA activity was highlighted, thereby suggesting potentially different modes of action of the different prenylated (iso)flavonoids.

Isolation of Lactic Acid Bacteria with Anti-MRSA Bacteriocin Activity and Characterization of the Bacteriocin Product

Isolation of Lactic Acid Bacteria with Anti-MRSA Bacteriocin Activity and Characterization of the Bacteriocin Product

Molecular Topology for the Search of New Anti-MRSA Compounds.

The variability of methicillin-resistant Staphylococcus aureus (MRSA), its rapid adaptive response against environmental changes, and its continued acquisition of antibiotic resistance determinants have made it commonplace in hospitals, where it causes the problem of multidrug resistance. In this study, we used molecular topology to develop several discriminant equations capable of classifying compounds according to their anti-MRSA activity. Topological indices were used as structural descriptors and their relationship with anti-MRSA activity was determined by applying linear discriminant analysis (LDA) on a group of quinolones and quinolone-like compounds. Four extra equations were constructed, named DFMRSA1, DFMRSA2, DFMRSA3 and DFMRSA4 (DFMRSA was built in a previous study), all with good statistical parameters, such as Fisher–Snedecor F (>68 in all cases), Wilk’s lambda (<0.13 in all cases), and percentage of correct classification (>94% in all cases), which allows a reliable extrapolation prediction of antibacterial activity in any organic compound. The results obtained clearly reveal the high efficiency of combining molecular topology with LDA for the prediction of anti-MRSA activity.

Chemistry and Pharmacology of Natural Catechins from Camellia sinensis as Anti-MRSA Agents.

Tea, a worldwide popular beverage rich in polyphenols, contributes to the prevention of many diseases and thus is beneficial to human health. Tea is a product through processing the fresh leaves picked from the plant Camellia sinensis (C. sinensis, genus Camellia section Thea). To date, systematic studies have been conducted on the phytochemicals from more than 20 tea varieties and related tea products, resulting in the structural determination of over 400 constituents viz. different types of polyphenols, purines, and their derivatives, mono to tetra-terpenoids, and minor other phytomolecules. These various tea phytochemicals contribute to the anti-oxidative effects, anti-diabetes, anti-inflammation, anti-cancer, blood lipid reduction, neuroprotection, anti-Alzheimer's disease, hepatoprotection, and anti-microbial activities, etc. Staphylococcus aureus (S. aureus), the significant human pathogens, could cause nosocomial and community-acquired infections, which is also responsible for various infectious diseases from mild to severe life-threatening conditions, such as bacteremia (bloodstream infection), endocarditis (heart valves infection), pneumonia, and meningitis (brain infection), leading to 2% clinical disease in of all patient admissions. The multidrug resistance (MDR) and antibiotics losing efficacy, esp. in methicillin resistance Staphylococcus aureus (MRSA) urge for novel antimicrobial agents. The MRSA strains are resistant to the entire class of β-lactam antibiotics and limit effective treatment, leading to still spread of staphylococcal infections. MRSA also exhibits resistance to cephalosporins, macrolides, fluoroquinolones, aminoglycosides, and glycopeptides (teicoplanine and vancomycin), leading to resistant strains-glycopeptide resistant strain (GRSA) and glycopeptide intermediate (GISA) S. aureus. In this review, chemical constituents responsible for the anti-MRSA activity of tea are explored.

Anti-MRSA activity of ethyl acetate crude extract from endophytic fungus Ceratobasidium ramicola IBRLCM127 isolated from rhizome of Curcuma mangga Valeton & Zijp

The study was conducted to investigate the effects of ethyl acetate crude extract of C. ramicola IBRLCM127, an endophytic fungus which was previously isolated from rhizome of C. mangga against a common human bacterial pathogen, methicillin-resistant Staphylococcus aureus (MRSA) in order to develop a new MRSA treatmet. The efficiency of antimicrobial compounds in inhibiting or killing the bacterial cells was evaluated by adopting minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC). The effect of ethyl acetate crude extract on the growth profile of MRSA was examined using time-kill assay. Scanning electron microscope (SEM) observation was opted to investigate the ultrastructural effect of MRSA cells. The results revealed that fungal extract demonstrated a bactericidal effect on MRSA with the ratio of MBC/MIC was 1. Both MIC and MBC values of the extract were 0.5 mg/mL. The result obtained from the time-kill study disclosed that the bactericidal activity of fungal extract under investigation was both time and concentration-dependent. After 12 hours of exposure to the extract, the formation of cavities and a few cell debris can be observed on the bacterial cells, indicating the failure of cell wall and cell membrane to maintain their rigid structure due to the rupture caused by the extract. Prolonged exposure to the extract for up to 48 hours caused the bacterial cell wall to lyse and release its cytoplasmic content into the surrounding which led to cell death. Based on the SEM observation, the fungal ethyl acetate extract of C. ramicola IBRLCM127 exhibited a prominent anti-MRSA activity particularly against cell membrane of MRSA cells. This report was the first report concerning the antimicrobial potential of endophytic fungus C. ramicola recovered from local medicinal plant, C. mangga.

Chromone Derivatives Of Cassia pumila and their Anti-MRSA Activity

Chromone Derivatives Of Cassia pumila and their Anti-MRSA Activity

Scopariusicide C, a novel cyclobutene-containing meroditerpenoid from artificially cultivated Isodon scoparius

Scopariusicide C (1), a novel ent-clerodane-based meroditerpenoid was isolated from artificially cultivated Isodon scoparius. An oxygen insertion reaction proposed to occur in its biosynthesis makes its scaffold different from those meroterpenoids previously isolated from the same species. The structure of 1 was determined by analysis of spectroscopic data, quantum chemical calculations and use of residual dipolar coupling (RDC). 1 showed moderate inhibitory effects against T and B lymphocyte proliferation and good anti-MRSA activity.

Anti-MRSA activity of curcumin in planktonic cells and biofilms and determination of possible action mechanisms

Staphylococcus aureus is a commensal bacterium and opportunistic human pathogen that can cause a wide variety of clinical infections. It is recognized for its ability to acquire antimicrobial resistance, so methicillin-resistant Staphylococcus aureus (MRSA) infections are a global healthcare challenge. Therefore, the development of new therapeutic options and alternative therapies for treatment is necessary. Curcumin, a polyphenolic substance found in the rhizome of turmeric longa L, has been shown to have several therapeutic properties, including antimicrobial activity. The objective of the study was to evaluate the in vitro antibacterial activity of curcumin alone and associated with oxacillin against MRSA strains, to analyze the mechanism of cell death involved in the isolated action of curcumin by means of flow cytometry and molecular docking, and to verify its superbiofilm action. Curcumin showed antibacterial activity in the range of 125–500 μg/mL against the tested strains, since it caused an increase in membrane permeability and DNA fragmentation, as revealed by flow cytometry analysis. Moreover, it was possible to observe interactions of curcumin with wild-type S. aureus DHFR, S. aureus gyrase and S. aureus gyrase complex with DNA, DNA (5′-D(*CP*GP*AP*TP*GP*CP*G)-3′) and Acyl-PBP2a from MRSA by molecular docking. Curcumin also had a synergistic and additive effect when associated with oxacillin, and significantly reduced the cell viability of the analyzed biofilms. Thus, curcumin is a possible candidate for pharmaceutical formulation development for the treatment of MRSA infections.

In Vitro Antibacterial, Anti-Adhesive and Anti-Biofilm Activities of Krameria lappacea (Dombey) Burdet & B.B. Simpson Root Extract against Methicillin-Resistant Staphylococcus aureus Strains.

Methicillin-resistant Staphylococcus aureus (MRSA) represents a serious threat to public health, due to its large variety of pathogenetic mechanisms. Accordingly, the present study aimed to investigate the anti-MRSA activities of Krameria lappacea, a medicinal plant native to South America. Through Ultra-High-Performance Liquid Chromatography coupled with High-Resolution Mass spectrometry, we analyzed the chemical composition of Krameria lappacea root extract (KLRE). The antibacterial activity of KLRE was determined by the broth microdilution method, also including the minimum biofilm inhibitory concentration and minimum biofilm eradication concentration. Besides, we evaluated the effect on adhesion and invasion of human lung carcinoma A549 cell line by MRSA strains. The obtained results revealed an interesting antimicrobial action of this extract, which efficiently inhibit the growth, biofilm formation, adhesion and invasion of MRSA strains. Furthermore, the chemical analysis revealed the presence in the extract of several flavonoid compounds and type-A and type-B proanthocyanidins, which are known for their anti-adhesive effects. Taken together, our findings showed an interesting antimicrobial activity of KLRE, giving an important contribution to the current knowledge on the biological activities of this plant.

Designing a leucine‐rich antibacterial nonapeptide with potent activity against mupirocin‐resistant MRSA via a structure–activity relationship study

Staphylococcus aureus is the main aetiological agent responsible for the majority of human skin infections. Of particular concern is the methicillin-resistant variety, commonly known as MRSA. The extensive use of the first-line topical antibiotic of choice, mupirocin, has inevitably resulted in the emergence of resistant strains, signalling an urgent need for the development of new antibacterials with new mechanisms of action. In this work, we describe how we designed a novel cationic nonapeptide, containing only leucine and two lysine residues, with potent anti-MRSA activity and a rapid bactericidal mode of action. Coupled to a favourable safety profile towards human skin fibroblasts, we believe nonapeptide 11 has high potential for further development as a mupirocin replacement candidate to treat skin infections caused by MRSA.

Antibacterial Naphthalene Derivatives from the Fermentation Products of the Endophytic Fungus Phomopsis fukushii

Two new naphthalene derivatives, 1-(3-hydroxy-1-(hydroxymethyl)-2-methoxy-6-methylnaphthalen-7-yl) propan-2-one (1) and 1-(3-hydroxy-1-(hydroxymethyl)-6-methylnaphthalen-7-yl)propan-2-one (2), together three known naphthalene derivatives (3–5) were isolated from the fermentation products of the endophytic fungus Phomopsis fukushii. Their structures were elucidated by spectroscopic methods, including extensive 1D and 2D NMR techniques. Compounds 1 and 2 were evaluated for their anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) activity. The results showed that compounds 1 and 2 showed weak inhibition with IZD of 10.2 ± 1.8 and 11.3 ± 2.0 mm, respectively.

Anti-MRSA Constituents from Ruta chalepensis (Rutaceae) Grown in Iraq, and In Silico Studies on Two of Most Active Compounds, Chalepensin and 6-Hydroxy-rutin 3',7-Dimethyl ether.

Ruta chalepensis L. (Rutaceae), a perennial herb with wild and cultivated habitats, is well known for its traditional uses as an anti-inflammatory, analgesic, antipyretic agent, and in the treatment of rheumatism, nerve diseases, neuralgia, dropsy, convulsions and mental disorders. The antimicrobial activities of the crude extracts from the fruits, leaves, stem and roots of R. chalepensis were initially evaluated against two Gram-positive and two Gram-negative bacterial strains and a strain of the fungus Candida albicans. Phytochemical investigation afforded 19 compounds, including alkaloids, coumarins, flavonoid glycosides, a cinnamic acid derivative and a long-chain alkane. These compounds were tested against a panel of methicillin-resistant Staphylococcus aureus (MRSA) strains, i.e., ATCC 25923, SA-1199B, XU212, MRSA-274819 and EMRSA-15. The MIC values of the active compounds, chalepin (9), chalepensin (10), rutamarin (11), rutin 3′-methyl ether (14), rutin 7,4′-dimethyl ether (15), 6-hydroxy-rutin 3′,7-dimethyl ether (16) and arborinine (18) were in the range of 32–128 µg/mL against the tested MRSA strains. Compounds 10 and 16 were the most active compounds from R. chalepensis, and were active against four out of six tested MRSA strains, and in silico studies were performed on these compounds. The anti-MRSA activity of compound 16 was comparable to that of the positive control norfloxacin (MICs 32 vs 16 μg/mL, respectively) against the MRSA strain XU212, which is a Kuwaiti hospital isolate that possesses the TetK tetracycline efflux pump. This is the first report on the anti-MRSA property of compounds isolated from R. chalepensis and relevant in silico studies on the most active compounds.

Discovery of Brominated Alboflavusins With Anti-MRSA Activities.

As methicillin-resistant Staphylococcus aureus (MRSA) is becoming a serious pathogenic threaten to human health worldwide, there is an urgent need to discover new antibiotics for the treatment of MRSA infections. Alboflavusins (AFNs) are a group of halogenated cyclohexapeptides with anti-MRSA activities. In this study, two novel brominated AFN congeners (compounds 1 and 2) were isolated from the wild-type strain Streptomyces alboflavus sp. 313 that was fermented in the production medium supplemented with NaBr; two new (compounds 3 and 5) and a known (compound 4) dehelogenated AFN congeners were isolated from S. alboflavus ΔafnX, in which the tryptophan halogenase gene afnX was inactivated. The structures of these compounds were assigned by careful NMR and MS analyses. The anti-MRSA activities of varied AFN congeners were assessed against different MRSA strains, which revealed that compounds 1 and 2 with bromine displayed effective activities against the tested MRSA strains. Especially, compound 2 showed good anti-MRSA activity, while compounds 3, 4, and 5 without halogen exhibited weak anti-MRSA activities, outlining the influence of halogen substitution to the bioactivities of AFNs.

Multifunctional lipid-based nanocarriers with antibacterial and anti\u2010inflammatory activities for treating MRSA bacteremia in mice

BackgroundBacteremia-induced sepsis is a leading cause of mortality in intensive care units. To control a bacterial infection, an immune response is required, but this response might contribute to organ failure. Kidneys are one of the main organs affected by bacteremia. Combination therapies with antibacterial and anti-inflammatory effects may be beneficial in treating bacteremia. This study aimed to develop nanostructured lipid carriers (NLCs) loaded with ciprofloxacin and rolipram that exert a combination of anti-methicillin-resistant Staphylococcus aureus (MRSA) and anti-inflammatory effects. Retinol was incorporated into the nanoparticles to transport retinol-binding protein 4 (RBP4) to the kidneys, which abundantly express RBP receptors. The NLCs were fabricated by high-shear homogenization and sonication, and neutrophils were used as a model to assess their anti-inflammatory effects. Mice were injected with MRSA to establish a model of bacteremia with organ injury.ResultsThe mean nanoparticle size and zeta potential of the NLCs were 171 nm and − 39 mV, respectively. Ciprofloxacin (0.05%, w/v) and rolipram (0.02%) achieved encapsulation percentages of 88% and 96%, respectively, in the nanosystems. The minimum bactericidal concentration of free ciprofloxacin against MRSA increased from 1.95 to 15.63 µg/ml when combined with rolipram, indicating a possible drug-drug interaction that reduced the antibacterial effect. Nanoparticle inclusion promoted the anti-MRSA activity of ciprofloxacin according to time-kill curves. The NLCs were found to be largely internalized into neutrophils and exhibited superior superoxide anion inhibition than free drugs. Retinol incorporation into the nanocarriers facilitated their efficient targeting to the kidneys. The NLCs significantly mitigated MRSA burden and elastase distribution in the organs of MRSA-infected animals, and the greatest inhibition was observed in the kidneys. Bacterial clearance and neutrophil infiltration suppression attenuated the bacteremia-induced cytokine overexpression, leading to an improvement in the survival rate from 22% to 67%.ConclusionsThe dual role of our NLCs endowed them with greater efficacy in treating MRSA bacteremia than that of free drugs.

Mollicellins S-U, three new depsidones from Chaetomium brasiliense SD-596 with anti-MRSA activities.

Fungi are important resources for drug development, as they have a diversity of genes, that can produce novel secondary metabolites with effective bioactivities. Here, five depsidone-based analogs were isolated from the rice media of Chaetomium brasiliense SD-596. Their structures were elucidated using NMR and mass spectrometry analysis. Five compounds, including three new depsidone analogs, mollicellin S (1), mollicellin T (2), and mollicellin U (3), and two known compounds, mollicellin D (4) and mollicellin H (5), exhibited significant inhibition against Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA), with MIC values ranging from 6.25 to 12.5 μg ml-1. Herein, we identified the predicted plausible biosynthetic cluster of the compounds and discussed the structure-activity relationship. Finally, we found that the introduction of aldehyde and methoxyl groups provide marked improvement for the inhibition against MRSA.