Analysis of the Antimicrobial and Anti-Biofilm Activity of Natural Compounds and Their Analogues against Staphylococcus aureus Isolates.

(1) Background: Staphylococcus aureus (S. aureus) is one of the most frequent causes of biofilm-associated infections. With the emergence of antibiotic-resistant, especially methicillin-resistant S. aureus (MRSA), there is an urgent need to discover novel inhibitory compounds against this clinically important pathogen. In this study, we evaluated the antimicrobial and anti-biofilm activity of 11 compounds, including phenyl propenes and phenolic aldehydes, eugenol, ferulic acid, sinapic acid, salicylaldehyde, vanillin, cinnamoyl acid, and aldehydes, against drug-resistant S. aureus isolates. (2) Methods: Thirty-two clinical S. aureus isolates were obtained from Alkhidmat Diagnostic Center and Blood Bank, Karachi, Pakistan, and screened for biofilm-forming potential, and susceptibility/resistance against ciprofloxacin, chloramphenicol, ampicillin, amikacin, cephalothin, clindamycin, streptomycin, and gentamicin using the Kirby-Bauer disk diffusion method. Subsequently, 5 representative clinical isolates were selected and used to test the antimicrobial and anti-biofilm potential of 11 compounds using both qualitative and quantitative assays, followed by qPCR analysis to examine the differences in the expression levels of biofilm-forming genes (ica-A, fnb-B, clf-A and cna) in treated (with natural compounds and their derivatives) and untreated isolates. (3) Results: All isolates were found to be multi-drug resistant and dominant biofilm formers. The individual Minimum Inhibitory Concentration (MIC) of natural compounds and their analogues ranged from 0.75−160 mg/mL. Furthermore, the compounds, Salicylaldehyde (SALI), Vanillin (VAN), α-methyl-trans-cinnamaldehyde (A-MT), and trans-4-nitrocinnamic acid (T4N) exhibited significant (15−92%) biofilm inhibition/reduction percentage capacity at the concentration of 1−10 mg/mL. Gene expression analysis showed that salicylaldehyde, α-methyl-trans-cinnamaldehyde, and α-bromo-trans-cinnamaldehyde resulted in a significant (p < 0.05) downregulation of the expression of ica-A, clf-A, and fnb-A genes compared to the untreated resistant isolate. (4) Conclusions: The natural compounds and their analogues used in this study exhibited significant antimicrobial and anti-biofilm activity against S. aureus. Biofilms persist as the main concern in clinical settings. These compounds may serve as potential candidate drug molecules against biofilm forming S. aureus.

Volatile constituents and in vitro activity of Syzygium aromaticum flower buds (clove) against human cancer cell lines.

The methanolic extract (SA-EXT) of Syzygium aromaticum flower buds and its fractions tested against three human cancer cell lines viz uterine cervix (HeLa), breast (MCF-7) and lung NCI (H-460) using sulforhodamine-B assay. The ethyl acetate soluble sub fraction (SA-EAS) was active only against HeLa cells with GI50value of 36± 3.4µg/mL. The most active sub-fraction (SA-PES-Fr-2) showed growth inhibition (GI50: 36, 50 and 68µg/ml against MCF-7, HeLa and NCI-H-460 cancer cell lines, respectively) with cytotoxic effect LC50= 88 ± 3.4 µg/mL against HeLa and LC50=86 ± 2.8 µg/mL against MCF-7. The most active sub-fraction (SA-PES-Fr-2) analyzed by GC and GC-MS techniques revealed that eugenol was most abundant (85.34%) along with minor constituents. Thus it can be concluded that growth inhibitory and cytotoxic effect residing in Syzygium aromaticum flower buds (clove) is more likely due to eugenol.

Triterpenoids from the aerial parts of Lantana camara.

Two new pentacyclic triterpenoids lancamarinic acid and lancamarinin have been obtained from the aerial parts of Lantana camara Linn. They were characterized as 22ß-acetoxy-3,25-epoxy-3α-hydroxyolean-12-en-28-oic acid and methyl 3,25-epoxy-3α-hydroxy-11-oxo-22ß-senecioyloxyolean-12-en-28-oate, respectively, through chemical transformation and exhaustive spectroscopic studies.

Synthesis and preparation of fluorinated polycarbonates enhancing the light absorption of fluorescent nanoparticles.

A new synthetic method for fluorinated polycarbonates without the use of any toxic phosgene gas is presented. The synthesis consists of a monomer synthesis followed by polymerization. The fluorinated polycarbonate (FPC) was confirmed by Fourier transform infrared spectroscopy (FT-IR) and NMR spectroscopy. The refractive index of the polymer was 1.466 determined by an Abbe refractometer. The contact angle measurement of the FPC films showed the hydrophobicity with water contact angle about 112.6 degrees. These films of varying thicknesses had over 98% transmittance. Taking advantage of the hydrophobicity and high transmittance of the FPCs, nanoparticles of FPCs were prepared directly in an aqueous solution with a reprecipitation method. Combining FPC solution with a solution containing fluorescent polymer (DTMSPV), nanoparticles with a core-shell structure were obtained easily with the reprecipitation method. The fluorescence intensity of the DTMSPV in the core-shell nanoparticles were much enhanced up to 34.1% compared to the molecularly dispersed DTMSPV solution.

An efficient synthesis of O- and N- alkyl derivatives of 4-aminobenzoic acid and evaluation of their anticancer properties.

A series of twenty alkyl derivatives (2-21) of 4-amino benzoic acid (1, PABA) have been prepared using potassium carbonate and opportune alkylating agents under simple and mild reaction conditions. Compounds (16-21) are reported for the first time. Electron impact mass spectrometry (EIMS), Fourier transform infrared (FTIR) and Proton nuclear magnetic resonance (1H-NMR) spectroscopic techniques were adopted for the characterization of these analogues. In the present study, the cytotoxic screening of sixteen compounds (3, 5-11, 13 and 15-21) was also achieved against lung (NCI-H460) and oral squamous carcinoma (CAL-27) cell lines. Compound 20 has shown magnificent inhibitory properties against NCI-H460 cell line (IC50 15.59 and 20.04 µM, respectively) at a lower dose than that of the control (cisplatin; IC50 21.00 µM). One-way analysis of variance (ANOVA), t-test and Pearson correlation coefficient (PCC) have been performed to determine the reliability of current data through statistical package for the social sciences (SPSS).

Synthesis, Characterization, DPPH Radical Scavenging, Urease Enzyme Inhibition, Molecular Docking Simulation, and DFT Analysis of Imine Derivatives of 4-formylpyridine with Selective Detection of Cu+2 Ions.

This study aimed to prepare three imine derivatives (1, 2, and 3) via a condensation reaction of phenyl hydrazine, 2-hydrazino pyridine, and 4-methoxy aniline with 4-formyl pyridine. Electron impact mass spectrometry (EIMS), proton nuclear magnetic resonance (1H-NMR), ultraviolet-visible (UV-Vis) and Fourier transform infrared (FTIR) spectroscopy were utilized for the characterization. The chemosensing properties of [4((2-phenyl hydrazono)methyl) pyridine] (1), [2-(2-(pyridin-4-ylmethylene)hydrazinyl) pyridine] (2), and [4-methoxy-N-yl methylene) aniline] (3) imino bases have been explored for the first time in aqueous media. The photophysical properties of chemosensors (1, 2, and 3) were examined by various cations (Na+, NH4+, Ba+2, Ni+2, Ca+2, Hg+2, Cu+2, Mg+2, Mn+2, and Pd+2). The chemosensor (1) showed very selective binding capability with copper ions at low concentrations (20 µM) without the influence of any other mentioned ions. The maximum complexation was noted with Cu+2 and 1 at pH between 7 to 7.5. The stoichiometry binding ratio between chemosensor (1) and Cu+2 was determined by Job's plot and it was found to be 1:2. The current study explored the use of these Schiff bases for the first time as heterocyclic chemosensors. DPPH radical scavenging, urease enzyme inhibition activities, molecular docking simulation, and density functional theory (DFT) analysis of compounds 1, 2, and 3 were also conducted.

3-Methyl-1H-pyrrolo[2,1-c][1,4]oxazin-1-one.

In the title mol-ecule, C(8)H(7)NO(2), all the non-H atoms lie essentially in the same plane (r.m.s. deviation = 0.019 Å) In the crystal structure, weak inter-molecular C-H⋯O inter-actions link mol-ecules into chains along [100]. In addition, there are π-π stacking inter-actions between mol-ecules related by the c-glide plane, with alternating centroid-centroid distances of 3.434 (2) and 3.639 (2) Å.

Di-tert-butyl cyclo-hex-2-ene-1,4-diyl dicarbonate.

In the title mol-ecule, C(16)H(26)O(6), the central cyclo-hexene ring is in a half-chair conformation. The carbonyl groups are in a trans arrangement with respect to each other and the dihedral angle between the mean planes of the carbonate groups is 10.8 (2)°.

A simple, rapid and mild one pot synthesis of benzene ring acylated and demethylated analogues of harmine under solvent-free conditions.

A simple, rapid, solvent-free, room temperature one pot synthesis of benzene ring acylated and demethylated analogues of harmine using acyl halides/acid anhydrides and AlCl(3) has been developed. Eight different acyl halides/acid anhydrides were used in the synthesis. The resulting mixture of products was separated by column chromatography to afford 10- and 12-monoacyl analogues, along with 10,12-diacyl-11-hydroxy products. In five cases the corresponding 10-acyl-11-hydroxy analogues were also obtained. Yields from the eight syntheses (29 products in total) were in the 6-34% range and all compounds were fully characterized.

A new ethylene glycol triterpenoid from the leaves of Psidium guajava.

One new pentacyclic triterpenoid psidiumoic acid (5) along with four known compounds beta-sitosterol (1), obtusol (2), oleanolic acid (3), and ursolic acid (4) have been isolated from the leaves of Psidium guajava. The new constituent 5 has been characterized as 2 alpha-glycolyl-3beta-hydroxyolean-12-en-28-oic acid through 2D NMR techniques. This is the first report of isolation of compound 2 from the genus Psidium.

Chemical constituents from the leaves of Psidium guajava.

Five constituents including one new pentacyclic triterpenoid guajanoic acid (1) and four known compounds beta-sitosterol (2), uvaol (3), oleanolic acid (4), and ursolic acid (5) have been isolated from the leaves of Psidium guajava. The new constituent 1 has been characterized as 3beta-p-E-coumaroyloxy-2alpha-methoxyurs-12-en-28-oic acid through 2D NMR techniques and chemical transformations. This is the first report of isolation of compound 3 from the genus Psidium.

Analgesic and anti-inflammatory activities of Piper nigrum L.

OBJECTIVE: To evaluate and compare the analgesic and anti-inflammatory activity of pure compound, piperine along with hexane and ethanol extracts of Piper nigrum L. fruit in mice and rats. METHODS: The analgesic activity was determined by tail immersion method, analgesy-meter, hot plate and acetic acid induced writhing test. While the anti-inflammatory activity was evaluated by carrageenan-induced paw inflammation in rats. RESULTS: Piperine at a dose of 5 mg/kg and ethanol extract at a dose of 15 mg/kg after 120 min and hexane extract at a dose of 10 mg/kg after 60 min exhibited significant (P<0.05) analgesic activity by tail immersion method, in comparison to ethanol extract at a dose of 10 mg/kg using analgesy-meter in rats. However, with hotplate method, piperine produced significant (P<0.05) analgesic activity at lower doses (5 and 10 mg/kg) after 120 min. A similar analgesic activity was noted with hexane extract at 15 mg/kg. However, in writhing test, ethanol extract significantly (P<0.05) stopped the number of writhes at a dose of 15 mg/kg, while piperine at a dose of 10 mg/kg completely terminated the writhes in mice. In the evaluation of anti-inflammatory effect using plethysmometer, piperine at doses of 10 and 15 mg/kg started producing anti-inflammatory effect after 30 min, which lasted till 60 min, whereas hexane and ethanol extracts also produced a similar activity at a slightly low dose (10 mg/kg) but lasted for 120 min. CONCLUSIONS: It is concluded from the present study that Piper nigrum L possesses potent analgesic and anti-inflammatory activities.