In vitro antibiofilm activity of the freshwater bryozoan Hyalinella punctata: a case study of Pseudomonas aeruginosa PAO1

The antibiofilm and possible antiquorum sensing effects against the strain Pseudomonas aeruginosa PAO1 of five crude extracts of the freshwater bryozoan Hyalinella punctata (Hancock, 1850) were evaluated in vitro for the first time. H. punctata ethyl acetate extract (HpEtAc) exhibited the highest antibiofilm activity reducing the biofilm formation of P. aeruginosa PAO1 in the range of 80.63–88.13%. While all tested extracts reduced the twitching motility of the aforementioned bacterial strain, HpEtAc showed to be the most effective. Finally, at a concentration of 0.5 MIC, the same extract mostly inhibited the production of pyocyanin by P. aeruginosa PAO1 (71.53%). In comparison both with the positive controls used (streptomycin and ampicillin, 67.13 and 69.77%, respectively), HpEtAc was found to inhibit pyocyanin in a higher extent. An extensive chemical characterisation of this particular extract may result in isolation and identification of novel lead compounds targeting P. aeruginosa, an opportunistic human pathogen.     

An insight into antimicrobial activity of the freshwater bryozoan Pectinatella magnifica

The antimicrobial activity of five crude extracts of the freshwater bryozoan Pectinatella magnifica (Leidy, 1851) was evaluated in vitro for the first time. P. magnifica acetone extract exhibited the highest antibacterial activity (minimum inhibitory concentrations (MIC) 0.004–0.350 mg/mL and MBC 0.007–0.500 mg/mL), while its methanol extract showed the most promising antifungal activity (MIC 0.03–0.12 mg/mL and MFC 0.06–0.25 mg/mL). Furthermore, at a concentration of 0.25 MIC, the methanol extract reduced biofilm formation of the bacterial strain Pseudomonas aeruginosa PAO1 in a considerable extent (59.14%). FTIR spectra of the most active extracts indicate the presence of carbonyl compounds, long-chain alcohols and/or sterols. According to the experimental data obtained, P. magnifica methanol extract may be considered as a good resource of novel natural products with potent antibiofilm activity against the bacterium well known for its resistance.     

Exploration of the Antimicrobial Effects of Benzothiazolylthiazolidin-4-One and In Silico Mechanistic Investigation

Background: Infectious diseases still affect large populations causing significant morbidity and mortality. Bacterial and fungal infections for centuries were the main factors of death and disability of millions of humans. Despite the progress in the control of infectious diseases, the appearance of resistance of microbes to existing drugs creates the need for the development of new effective antimicrobial agents. In an attempt to improve the antibacterial activity of previously synthesized compounds modifications to their structures were performed. Methods: Nineteen thiazolidinone derivatives with 6-Cl, 4-OMe, 6-CN, 6-adamantan, 4-Me, 6-adamantan substituents at benzothiazole ring were synthesized and evaluated against panel of four bacterial strains S. aureus, L. monocytogenes, E. coli and S. typhimirium and three resistant strains MRSA, E. coli and P. aeruginosa in order to improve activity of previously evaluated 6-OCF₃-benzothiazole-based thiazolidinones. The evaluation of minimum inhibitory and minimum bactericidal concentration was determined by microdilution method. As reference compounds ampicillin and streptomycin were used. Results: All compounds showed antibacterial activity with MIC in range of 0.12–0.75 mg/mL and MBC at 0.25–>1.00 mg/mL The most active compound among all tested appeared to be compound 18, with MIC at 0.10 mg/mL and MBC at 0.12 mg/mL against P. aeruginosa. as well as against resistant strain P. aeruginosa with MIC at 0.06 mg/mL and MBC at 0.12 mg/mL almost equipotent with streptomycin and better than ampicillin. Docking studies predicted that the inhibition of LD-carboxypeptidase is probably the possible mechanism of antibacterial activity of tested compounds. Conclusion: The best improvement of antibacterial activity after modifications was achieved by replacement of 6-OCF₃ substituent in benzothiazole moiety by 6-Cl against S. aureus, MRSA and resistant strain of E. coli by 2.5 folds, while against L. monocytogenes and S. typhimirium from 4 to 5 folds.     

Microwave-assisted synthesis and antibacterial activity of derivatives of 3-[1-(4-fluorobenzyl)-1H-indol-3-yl]-5-(4-fluorobenzylthio)-4H-1,2,4-triazol-4-amine

Herein, an excellent method for the synthesis of twelve novel Schiff base derivatives containing indole and triazole assisted by microwave irradiation is reported. Compared with the conventional method, the yields increased from 59–84 % to 85–96 % and the reaction time was reduced from 24–30 h to 4–8 min. Moreover, all series of the newly synthesized Schiff bases were evaluated for their antibacterial activity. The values of minimum inhibitory concentration (MIC) and IC50 indicated that many target compounds possessed excellent antibacterial activity against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Bacillus subtilis.     

Antibacterial and cytotoxic activities of phenolic constituents from the stem extracts of Spatholobus parviflorus

Abstract

A new 2-arylbenzofuran, spathobenzofuran (1), together with ten known compounds including a 2-arylbenzofuran, three pterocarpans and six isoflavones were isolated from the acetone crude extract of the stems of Spatholobus parviflorus. All compounds were characterised by spectroscopic methods. Compound 4 was active (MIC 8?µg/mL) against Gram-negative Pseudomonas aeruginosa TISTR 781 while compound 2 had modest activity against Gram-positive Staphylococcus aureus TISTR 1466 with a MIC value of 16?µg/mL. All isolated compounds showed no cytotoxicity against Vero and KB cells.     

Fluorescein dye derivative: Synthesis,characterization, quantum chemical and promising antimicrobial activity studies

The dimethyl sulfite as an alkylating as well as alkoxylating reagent is well known in synthetic organic as well as organometallic chemistry for a long time. Herein, we have utilized dimethyl sulfite as an alkylating reagent and reacted with fluorescein derivative, N-fluorescein-lactam-hydrazine ( B ). This reaction leads to the generation of tetramethylated fluorescein lactam hydrazine ( A ). The newly designed and synthesized molecule ( A ) has been characterized by ¹H, ¹³C NMR and HRMS data. The antimicrobial activity of the synthesized alkylated fluorescein derivative has been tested against E. coli, P. aeruginosa, Salmonella typhimurium and S. aureus microbial agents. Time-kill assay results also confirmed that fluorescein derivative is a potent antimicrobial agent and revealed that the time-kill assay of fluorescein derivative is value-added than the well-known antibiotic. In addition, quantum chemical study was used to analyze its activity trend and correlated with the experimental data. The computed results of DFT revealed that the lipophilicity as well as the LUMO-HOMO band gap (ΔE_LUMO-HOMO = 4.75 eV) of compound A make it more suitable as an antimicrobial agent to match with in vitro antimicrobial experimental results. The MIC and MBC values of compound A were observed to be lower in contrast to fluorescein and ampicillin for all the tested bacterial strains, which were approximately 3- to 4-fold lower than MIC and MBC values of the later. Results obtained from the study clearly indicate that compound A has better antimicrobial and bactericidal activity in comparison to ampicillin and fluorescein. Synthesized compound can be a better substitute of traditionally used antibiotics, Ampicillin.     

Inhibition of Quorum Sensing,Motility and Biofilm Formation of Pseudomonas aeruginosa by Copper Oxide Nanostructures

Quorum sensing (QS) is the communication between bacterial cells governed by their population density and regulated by the genes controlling virulence factors and biofilm formation. Multiple mechanisms of biofilms are resistive to antimicrobial chemotherapy; therefore novel strategies are required to overcome its limitations. Here, we report the effect of various copper oxide nanostructures (CuO-NSs) on quorum sensing inhibition. The two-dimensional CuO-NSs such as interlaced nanodiscs, nanodiscs and leaf-shaped nanosheets are prepared via a simple chemical method. The Quorum sensing inhibition (QSI) activity of all the CuO-NS are examined using reporter strain Chromobacterium violaceum CV026 and Escherichia coli pSB1142. We found that the CuO-interlaced nanodisc structures exhibit better QSI activity than nanodiscs and leaf-shaped sheets. The interlaced nanodisc structures are inhibited various long-chain N-acyl homoserine lactones (AHLs) mediated QS individually and confirmed by other QS-associated phenomena for Pseudomonas aeruginosa, including biofilm inhibition, inhibition of virulence factors such as pyocyanin, protease production and swarming motility. Thus QSI activity of CuO-NSs is solely dependent on specific shape offering large surface area and more active sites. The CuO-NS is effective quorum sensing inhibitors, which has potential clinical applications in the management of P. aeruginosa associated infections.

     

Chemical Composition Analysis and Antimicrobial Screening of the Essential Oil of a Rare Plant from Jordan: Ducrosia flabellifolia

The composition of the essential oil isolated from the fresh and dry leaves of Ducrosia flabellifolia Boiss. (Apiaceae) was determined by gas chromatography and gas chromatography–mass spectrometry using hydrodistillation and solid phase microextraction (SPME). The hydrodistilled oil of the fresh leaves yielded 38 components, accounting for 98.67% of the total oil content, while thirty components were detected from the fresh leaves by solid phase microextraction (94.85%). Fifty-one and 36 components were identified in the hydrodistilled and SPME oils of the dried leaves amounting to 98.78% and 94.52%, respectively. A total of 25 components accounting for 97.24% of the total composition were characterized in the SPME oil of the fresh flowers. Aliphatic compounds predominated in the volatile fractions of the leaves and flowers of both methods with n-decanol, n-decanal, and dodecanal as the main constituents. The α- and ß-pinene were the major monoterpenoids in the oils. The hydrodistilled oil was screened for its antimicrobial and antioxidant activities. The minimal inhibitory concentration of the volatile oil was determined using a microdilution method in 96 well plates against a panel of gram (+), gram (?) bacteria, and fungi. Overnight cultures of reference strains of Candida albicans, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus were used as test microorganisms. The oil exhibited the best activity against C. albicans (MIC 234 µg/mL) and S. aureus (MIC 234 µg/mL) whereas weak activity was detected against E. coli and P. aeruginosa. No antioxidant activity could be detected.     

Bioactive DOPA melanin isolated and characterised from a marine actinobacterium Streptomyces sp. MVCS6 from Versova coast

The melanin pigment produced from Streptomyces sp., MVCS6 was isolated and dihydroxyphenyalanine (DOPA) melanin compound was biochemically identified and spectroscopically characterised (ultraviolet and FT-IR). DOPA melanin showed a promising activity as an antibacterial natural product against 12 pathogenic bacteria from hospital isolations, particularly, against Pseudomonas aeruginosa RMMH7 (inhibition zone of 18 ± 0.02 at 30 μg/disc, and MIC of 10 ± 0.02 μg/mL) and Vibrio parahaemolytics RMMH12 (inhibition zone of 15 mm ± 0.03 at 30 μg/disc, and MIC of 14 ± 0.02 μg/mL). Moreover, in vitro evaluation of reducing power (Ascorbic Acid Equivalent (160 μg/mL)), DPPH radical-scavenging (89%), NO-scavenging (72%) and lipid peroxidation activities (89.6%) were determined. Cytotoxicity of DOPA melanin against cervical cancer cell line showed a dose–response activity, and IC₅₀ value was found to be 300 μg/mL. These results would open the way to propose Streptomyces sp. MVCS6 as a promising source of bioactive eumelanin with therapeutic potential in medicine.     

Quorum sensing inhibitors from marine bacteria Oceanobacillus sp. XC22919

In this study, three active compounds isolated from Oceanobacillus sp. XC22919 were identified as 2-methyl-N-(2′-phenylethyl) butyramide (1), 3-methyl-N-(2′-phenylethyl)-butyramide (2) and benzyl benzoate (3), and were first reported to exhibit the apparent quorum sensing inhibitory activities against C. violaceum 026 and P. aeruginosa. Compounds 1–3 inhibited violacein production of C. violaceum 026 by 10.5–55.7, 11.2–55.7, and 27.2%–95.7%, respectively, and inhibited pyocyanin production of P. aeruginosa by 1.7–50.8, 39.1–90.7, and 57.2%–98.7%, respectively. The azocasein-degrading proteolytic rates of P. aeruginosa were observed by 13.4–31.5, 13.4–28.8, and 11.3%–21.1%, respectively. With respect to elastase, the range of inhibition of activity of compounds 1–3 was 2.1–30.3, 4.2–18.2, and 8.9%–15.7%, respectively. Compounds 1 and 3 also showed a concentration-dependent attenuation in biofilm formation, with the maximum of 50.6% inhibition, and 37.7% inhibition at 100 μg/mL, respectively.     

Synthesis and discovery of N-(1-methyl-4-oxo-4,5-dihydro-1H-imidazol-2-yl)-[1,1′-biphenyl]-2-carboxamide derivatives as antimicrobial agents

Novel dihydro-1H-imidazole-2-yl)-[1,1′-biphenyl]-2-carboxamides ( 4a-l ) was achieved using a three-step synthesis process and evaluated as antimicrobial agents. These compounds were characterized through FTIR, NMR, LCMS and evaluated for DNA gyrase inhibition potentials and antimicrobial properties against Gram-negative bacteria Escherichia coli (MTCC 443), Pseudomonas aeruginosa (MTCC 424), Klebsiella pneumoniae MTCC 530 and Gram-positive bacteria Staphylococcus aureus (MTCC 3160), Corynebacterium diphtheriae (MTCC 116) and Streptococcus pyogenes (MTCC 442). Excellent DNA gyrase inhibition exhibited by compound 4f (IC₅₀ 0.2 μM and relative percentage activity 96.24%). A broad spectrum of antimicrobial activity showed by compounds 4d , 4f and 4 k with a Minimal Inhibitory Constant (MIC) of 1.05, 1.35 and 1.25 μg mL⁻¹, respectively.     

Chemical composition and antibacterial activity of the essential oil from Agathis dammara (Lamb.) Rich fresh leaves

The essential oil of fresh leaves from Agathis dammara (Lamb.) Rich was extracted using hydro-distillation, and GC-FID and GC–MS were used to analyse the essential oil. Nineteen compounds were identified, among which the major components were limonene (36.81%), β-bisabolene (33.43%) and β-myrcene (25.48%). In the antibacterial test, disc diffusion method and micro-well dilution assay proved that the essential oil had significant antibacterial activities. The inhibition zones against Staphylococcus aureus and Pseudomonas aeruginosa were 23.7 and 23 mm, respectively, which demonstrated that the inhibition effects were greater than positive control (10 μg/disc streptomycin). And the lowest MIC value of the essential oil was found against S. aureus (1.25 mg/mL) and Bacillus subtilis (1.25 mg/mL). This is the first report on the antibacterial activities of A. dammara essential oil.     

Stereoselective synthesis of the lichen metabolite, (+) montagnetol and its congeners as antimicrobial agents

Abstract

In view of structural diversity, (+) montagnetol, the major metabolite of the fruticose lichen, Roccella montagnei was synthesized along with three of its congeners by employing highly efficient protocols. (+) Montagnetol (2?R, 3S; 11) and (-) montagnetol (2S, 3R; 5) were synthesized in 7 and 9 steps, respectively, from L-ascorbic acid. The two new congeners 3 (2?R, 3R) and 6 (2S, 3S), which differ in configuration at C-2 and C-3 positions of the (+) montagnetol, were synthesized from (?) diethyl D-tartrate and (+) diethyl L-tartrate, respectively. The synthesized compounds were evaluated in vitro for antimicrobial activity against two Gram-positive (S. aureus and E. coli) and two Gram-negative (S. typhi and P. aeruginosa) bacteria and one fungal strain Candida albicans. Interestingly, the congener 3 showed promising anti-bacterial activity (MIC: 0.062?µg/ml) against P. aeruginosa, whereas the congener 6 displayed potent anti-fungal activity (MIC: 0.062?µg/ml) against C. Albicans.     

A new antibacterial lupane ester from the seeds of Acokanthera oppositifolia Lam.

As a part of ongoing investigation of Acokanthera oppositifolia (Lam.) Codd., four compounds were isolated from its seeds, a new compound; lup-20(29)-en-3β-O-(3′-β-hydroxy) palmitate (1), three known compounds; a triterpene; lupeol (2), a cardiac glycoside; acovenoside A (3) and a sterol; β-sitosterol (4). Their structures were investigated using 1D & 2D- ¹H and ¹³CNMR spectroscopy. Antimicrobial potential of the compounds was evaluated against 10 microorganisms responsible for endocarditis. The minimum inhibitory concentration (MIC) of the compounds was determined using broth microdilution method. The new compound (1) evidenced significant antibacterial activity especially aganist Pseudomonas aeruginosa with (MIC 7.81 μg/ml). Lupeol (2) exhibited remarkable antimicrobial activity against Methicillin-resistant Staphylococcus aureus, Aspergillus fumigates and Candida albicans (MIC 3.9, 0.24 and 3.9 μg/ml, respectively). On the other hand, acovenoside A (3) inhibited the growth of Escherichia coli (MIC 0.98 μg/ml). We herein present the potential of A. oppositifolia as a cardioprotective agent against the microorganisms responsible for endocarditis.     

Antimicrobial evaluation of selected naturally occurring oxyprenylated secondary metabolites

This study tested the antimicrobial activity of eight selected naturally occurring oxyprenylated secondary metabolites against Staphylococcus aureus ATCC 29213, S. epidermidis ATCC 35984, Escherichia coli ATCC 8739, Pseudomonas aeruginosa ATCC 9027 and Candida albicans ATCC 10231. Results showed a moderate antimicrobial activity. The most active compounds were 3-(4-geranyloxyphenyl)-1-ethanol (4) and 3-(4-isopentenyloxyphenyl)-1-propanol (5) that were tested on mature and in-formation biofilms of all micro-organisms, moreover the cytotoxic activity was evaluated. Except for S. epidermidis, both compounds reduced significantly (p < 0.05) the microbial biofilm formation at 1/2 MIC and 1/4 MIC, in particular, compounds 4 and 5 at each concentration, inhibited E. coli biofilm formation to a greater extent, the biofilm formation was never more than 44% in respect to the control, moreover both compounds showed a low cytotoxic effect. Oxyprenylated derivatives may be of great interest for the development of novel antimicrobial therapeutic strategies and the synthesis of semi-synthetic analogues with anti-biofilm efficacy.     

Novel Pyrazoline‐based Organometallic Compounds Containing Ferrocenyl and Quinoline units: Synthesis,Characterization and Microbial susceptibilities

Some novel pyrazoline‐based organometallic compounds were synthesized as new leads in antimicrobial chemotherapy. The structures of compounds were elucidated by different spectroscopic techniques and elemental analyses. All compounds were investigated for in vitro antimicrobial studies against fifteen ATTC bacterial and fungal strains. The microbial susceptibility of these compounds revealed that all the tested compounds gave good minimum inhibitory concentration (MIC) values against the tested organisms that are either similar or even better than the reference drugs amoxicillin and fluconazole, which gave MIC values 8‐64 μg/ml against bacterial and 64 μg/ml against fungal strains, respectively. Among all compounds, compound ( 4d ) 1‐(5‐(4‐chlorophenyl)‐3‐ferrocenyl‐4,5‐dihydropyrazol‐1‐yl)‐2‐quinolin‐8‐yloxy) ethanone, emerged out the most promising antimicrobial organometallic derivative with MIC values against all the strains ranging from 8‐32 μg/ml. Other compounds gave a range of MIC values between 16‐64 μg/ml against S. bovis, 16‐32 μg/ml against E. coli, and C. tropicalis except compound ( 4d) which gave MIC 8 μg/ml against S. bovis and E. coli, whereas 32 μg/ml against C. tropicalis. Collectively, these compounds gave a lower MIC value between 32‐64 μg/ml against both of the biofilm forming strains namely, P. aeruginosa and S. mutans. The results of microbial susceptibility concluded that these novel organometallic compounds are new leads in antimicrobial chemotherapy and can be very useful for further optimization work on microbial chemotherapy.     

In vitro interactions of Peucedanum officinale essential oil with antibiotics

The chemical composition and antibacterial activity of Peucedanum officinale L. (Apiaceae) essential oil were examined, as well as the association between it and antibiotics: tetracycline, streptomycin and chloramphenicol. The interactions of the essential oil with antibiotics were evaluated using the microdilution checkerboard assay. Monoterpene hydrocarbons, with α-phellandrene as the dominant constituent, were the most abundant compound class of the essential oil of P. officinale. The researched essential oil exhibited slight antibacterial activity against the tested bacterial strains in vitro. On the contrary, essential oil of P. officinale possesses a great synergistic potential with chloramphenicol and tetracycline. Their combinations reduced the minimum effective dose of the antibiotic and, consequently, minimised its adverse side effects. In addition, investigated interactions are especially successful against Gram-negative bacteria, the pharmacological treatment of which is very difficult nowadays.     

Chemical composition and antibacterial activity of the essential oil from Pyrrosia tonkinensis (Giesenhagen) Ching

The present study aimed to analyse the chemical components of the essential oil from Pyrrosia tonkinensis by GC-MS and evaluate the in vitro antibacterial activity. Twenty-eight compounds, representing 88.1% of the total essential oil, were identified and the major volatile components were trans-2-hexenal (22.1%), followed by nonanal (12.8%), limonene (9.6%), phytol (8.4%), 1-hexanol (3.8%), 2-furancarboxaldehyde (3.5%) and heptanal (3.1%). The antibacterial assays showed that the essential oil of P. tonkinensis had good antibacterial activities against all the tested microorganisms. This paper first reported the chemical composition and antimicrobial activity of the essential oil from P. tonkinensis.     

N,N′-(hexane-1,6-diyl)bis(N-((1-aryl/alkyl-1H-1,2,3-triazol-4-yl)methyl)-4-methyl benzenesulfonamide): Synthesis,antibacterial, antioxidant,and DNA-cleavage activities

Thirteen novel bis-1,2,3-triazole derivatives were synthesized under copper (I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition of N,N′-(hexane-1,6-diyl)bis(4-methyl-N-(prop-2-yn-1-yl)benzenesulfonamide) with different aryl azides and evaluated their biological activity. All the newly synthesized compounds were confirmed by ¹H-NMR, infrared, and elemental analysis and mass spectral studies. The synthesized bis-1,2,3-triazoles were evaluated for their antioxidant activity, and some of them were found to exhibit good to excellent antioxidant activity (IC₅₀: 11.13 ± 1.5 to 98.98 ± 1.7 μM) in comparison with standard references, Trolox (11.73 ± 1.5 μM) and ascorbic acid (3.34 ± 1.8 μM). The bistriazoles also exhibited excellent-to-moderate anti-bacterial activity (MIC: 2.253 to 75 µg mL^?1 against Bacillus subtilis, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa when compared with streptomycin. N,N′-(hexane-1,6-diyl)bis(N-((1-(3,5-dimethylphenyl)-1H-1,2,3-triazol-4-yl)methyl)-4-methyl benzenesulfonamide) has completely cleaved the DNA at a concentration of 100 mg mL^?1, and the remaining compounds have partially cleaved the DNA.     

Design,synthesis, anticancer,antibacterial, and antifungal evaluation of 4-aminoquinoline-1,3,5-triazine derivatives

A series of 4-aminoquinoline 1,3,5-triazine derivatives were synthesized and evaluated for anticancer activity against cancer cell lines HeLa, MCF-7, HL-60, HepG2 where these derivatives exert significant anticancer activity. The molecules found nontoxic against MCF-12A. The molecules also showed potent inhibition of EGFR-TK as compared to eroltinib in enzyme-based assay. The newly synthesized derivatives were screened for their in vitro antibacterial and antifungal activity against Bacillus subtilis, Bacillus cereus, Staphylococcus aureus, Proteus vulgaris, Escherichia coli, Pseudomonas aeruginosa and Candida albicans, Aspergillus niger, Aspergillus fumigatus using cefixime and fluconazole as standard. Antibacterial screening results suggest that compound 7c showed potent activity against S. aureus, P. aeruginosa, and P. vulgaris. In antifungal screening, compound 7b showed significant activity against A. niger, A. fumigatus and moderate activity against C. albicans.