Exploring the decolorization efficiency and biodegradation mechanisms of different functional textile azo dyes by Streptomyces albidoflavus 3MGH.

Efficiently mitigating and managing environmental pollution caused by the improper disposal of dyes and effluents from the textile industry is of great importance. This study evaluated the effectiveness of Streptomyces albidoflavus 3MGH in decolorizing and degrading three different azo dyes, namely Reactive Orange 122 (RO 122), Direct Blue 15 (DB 15), and Direct Black 38 (DB 38). Various analytical techniques, such as Fourier Transform Infrared (FTIR) spectroscopy, High-Performance Liquid Chromatography (HPLC), and Gas Chromatography-Mass Spectrometry (GC-MS) were used to analyze the degraded byproducts of the dyes. S. albidoflavus 3MGH demonstrated a strong capability to decolorize RO 122, DB 15, and DB 38, achieving up to 60.74%, 61.38%, and 53.43% decolorization within 5 days at a concentration of 0.3 g/L, respectively. The optimal conditions for the maximum decolorization of these azo dyes were found to be a temperature of 35 °C, a pH of 6, sucrose as a carbon source, and beef extract as a nitrogen source. Additionally, after optimization of the decolorization process, treatment with S. albidoflavus 3MGH resulted in significant reductions of 94.4%, 86.3%, and 68.2% in the total organic carbon of RO 122, DB 15, and DB 38, respectively. After the treatment process, we found the specific activity of the laccase enzyme, one of the mediating enzymes of the degradation mechanism, to be 5.96 U/mg. FT-IR spectroscopy analysis of the degraded metabolites showed specific changes and shifts in peaks compared to the control samples. GC-MS analysis revealed the presence of metabolites such as benzene, biphenyl, and naphthalene derivatives. Overall, this study demonstrated the potential of S. albidoflavus 3MGH for the effective decolorization and degradation of different azo dyes. The findings were validated through various analytical techniques, shedding light on the biodegradation mechanism employed by this strain.

Insight into antioxidant and anti-inflammatory effects of marine bacterial natural exopolysaccharide (EPSSM) using carrageenan-induced paw edema in rats.

Inflammation is a part of the body's intricate biological reaction to noxious stimuli and defensive reactions. So, the aim of this investigation was to study the anti-inflammatory activity of exopolysaccharide (EPSSM) using carrageenan-induced paw edema in rats. A halophilic bacterial strain was isolated from marine sediments in the Red Sea in Egypt. The isolate has been visually and physiologically recognized, as well as by analyzing its 16S rRNA gene, which confirms Kocuria sp. clone Asker4. This particular isolate can be referenced using the accession number OL798051.1. EPSSM was subjected to purification and fractionation by a DEAE-cellulose column. Preliminary chemical analysis of EPSSM indicated that the monosaccharides were fructose, glucuronic acid, and xylose, with 2.0, 0.5, and 1.0, respectively. The antioxidant potential of EPSSM was investigated, and it was discovered that the level of activity increased independently of the concentrations, reaching a maximum threshold of 94.13% at 100 µg/mL of EPSSM for 120 min. Also, EPSSM at 50 mg/kg orally produced a significant anti-inflammatory effect on the carrageenan model at 2, 3, and 4 intervals. The EPSSM intervention resulted in reductions in the levels of catalase and superoxide dismutase enzymes, as well as a decrease in glutathione. Furthermore, the levels of nitric oxide, lipid peroxidation, and reactive oxygen species resulting from carrageenan-induced edema showed a significant reduction subsequent to the administration of EPSSM. Moreover, the findings indicated that the protein expression levels of cyclooxygenase-2 and interleukin-6 were reduced following treatment with EPSSM, resulting in a reduction of paw edema.

Structural, dielectric, and antimicrobial evaluation of PMMA/CeO2 for optoelectronic devices.

In the current report, we have successfully synthesized nanocomposites of PMMA incorporating different doping of CeO2 through a chemical approach. XRD results reflects decent matching for CeO2 nanoparticles with 29 nm crystallite size. FTIR spectroscopy demonstrates the characteristic functional groups validating the successful formation of the composite. The optical study of PMMA and the nanocomposites has proven that the optical properties such as band gap, refractive index, optical permittivity, and loss tangent factor are affected by adding CeO2 to the PMMA matrix.The peak residing around 420 nm by UV measurements is allocated to occurring electrons photoexcitation from the valence to conduction band inherent in CeO2. The dielectric measurements were achieved using broadband dielectric spectroscopy upon a wide span of frequencies (10-1-107 Hz) and within temperatures from - 10 to 80 °C with a step of 10 °C. The permittivity decreases by adding CeO2 and the dielectric parameters are thermally enhanced, however, the temperature influence is based on CeO2 content, the higher the CeO2 amount, the higher the influence of temperature. The results of the nanocomposites revealed antibacterial activity counter to gram-positive bacteria strain (S. aureus, and B. subtilis), and gram-negative bacteria (E. coli, and K. pneumoniae), yeast (C. albicans, as well as fungi (A. niger). Inherently, the change in CeO2 concentration from 0.01 to 0.1 wt% delivers maximum influence against gram-negative bacteria. These PMMA CeO2-doped composites are beneficial for optoelectronic areas and devices.

Environmentally benign liquid chromatographic method for concurrent estimation of four antihistaminic drugs applying factorial design approach.

In the last few decades, green analytical chemistry (GAC) has become a smart magical solution for the qualification and quantification of many drugs. In the current study, a direct, sensitive, and green RP-HPLC method was used to separate three anti-histaminic combinations rupatadine/montelukast, desloratadine/montelukast, fexofenadine/montelukast, and finally a mixture of rupatadine and its metabolite; desloratadine in less than 20 min. The developed method was optimized by a 23 full factorial design to improve the chromatographic responses. The proposed method was used to analyze these antihistaminic combinations at different pharmaceutical ratios. The linearity range is from 1 to 10 µg/mL for rupatadine, desloratadine, and montelukast, while for fexofenadine from 1 to 24 µg/mL drugs. The proposed method is useful in common quality control analysis of the investigated quaternary combinations because of its non-toxic and eco-friendly effects on the environment and human beings. The proposed procedure was thoroughly validated in accordance with ICH guidelines and was revealed to be accurate, reproducible, and selective. The developed methods were compared with a reported reference comparison method, where no significant difference was observed.

Smart green spectrophotometric assay of the ternary mixture of drotaverine, caffeine and paracetamol in their pharmaceutical dosage form.

Three green and facile spectrophotometric methods were developed for the assay of Petro® components; drotaverine HCl (DRT), caffeine (CAFF), and paracetamol (PAR). The three methods depend on measuring the absorbance of the studied drugs through their ethanolic solution. The first derivative spectrophotometry (FDS) at (Δλ = 10) were good parameters for DRT and CAFF resolution; DRT and CAFF could be well calibrated using FDS at 320 and 285 nm, respectively. PAR could be estimated at 308 nm utilizing the second derivative spectrophotometry (SDS). Method II relies on the double divisor ratio derivative spectroscopy (DDRDS). The first derivative was applied on each drug where they would be assayed at 309, 288, and 255 nm for DRT, CAFF, and PAR, respectively. Method III depends on the mean centering (MCR) technique. DRT, CAFF, and PAR could be determined at 309, 214, and 248 nm, respectively. The concentrations were rectilinear in the ranges of 2-20 µg/mL for DRT, 1.5-15 µg/mL for CAFF, and 2-40 µg/mL for PAR in double devisor and mean centering but PAR from 5 to 40 µg/mL in derivative method. Method validation was performed according to ICH guidelines assured by the agreement with the comparison method. In addition, greenness assessment of the proposed methods was investigated. The application of the proposed method was extended to analyse tablet dosage form and performing invitro dissolution testing.

Spectrofluorometric determination of orphenadrine, dimenhydrinate, and cinnarizine using direct and synchronous techniques with greenness assessment.

Orphenadrine (ORP), dimenhydrinate (DMN), and cinnarizine (CNN) were investigated using green-sensitive spectrofluorometric methods. Method, I used for determination of DMN in 0.1 M hydrochloric acid (HCl) and 1.0% sodium dodecyl sulphate (SDS) at 286 nm after λex 222 nm, while for determination of ORP in 1.0% w/v SDS involves measuring the fluorescence at 285 nm after λex 220 nm. For DMN and ORP, the detection and quantitation limits were 2.99 and 4.71 and 9.08 and 14.29 ng/mL, respectively. The ranges of DMN and ORP were 0.10-1.0 and 0.04-0.5 µg/mL, respectively, in micellar aqueous solution. Method II, the derivative intensities of DMN and CNN were measured at a fixed of different wavelength between the excitation and the emission wavelengths (Δλ) = 60 nm at 282 and 322 nm, at the zero crossing of each other, respectively. The detection and quantitation limits for DMN and CNN were 1.77 and 0.88 ng/mL and 5.36 and 2.65 ng/mL, correspondingly, through the entire range of 0.1-1.0 µg/mL for DMN and CNN. The linearity was perfectly determined through the higher values of the correlation coefficient ranging from 0.9997 to 0.9999 for both direct and synchronous methods. The precision of the proposed methods was also confirmed via the lower values of the standard deviation which ranged from 0.39 to 1.11. The technique was expanded to analyze this mixture in combined tablets and laboratory-prepared mixtures. The method validation was done depending on the international conference on harmonization (ICH) recommendations. An analysis of the statistical data revealed a high agreement between the proposed data and the comparison methodology. Three different assessment methods demonstrated the greenness of the technique.

Characterization and in-vitro Alzheimer's properties of exopolysaccharide from Bacillus maritimus MSM1.

Four bacterial isolates were obtained from marine sediments collected from Sahl Hashish, Hurghada Red Sea, Egypt. This study was designed to search for promising anti-Alzheimer natural polysaccharide; therefore, four isolates were screened for exopolysaccharides (EPSs) production and acetylcholinesterase inhibition. The isolate S16 provided the highest EPS yield (7.51 g/L) and acetylcholinesterase inhibition. It was identified morphologically and genetically using 16S rRNA gene sequence analysis as Bacillus maritimus. A Physicochemical analysis of S16 exopolysaccharide (BMEPS) was estimated, which pointed to the presence of uronic acid and sulfate (24.7% and 18.3%, respectively). HPLC analysis indicated that mannuronic acid, glucuronic acid, glucose, and mannose are presented in a molar ratio of 0.8:1.0:2.8:2.3, respectively. Furthermore, FT-IR revealed an abundance of ß-configurations. The GPC estimated the average molecular weight (Mw) as 4.31 × 104 g/mol. BMEPS inhibited AChE (IC50; 691.77 ± 8.65 µg/ ml), BChE (IC50; 288.27 ± 10.50 µg/ ml), and tyrosinase (IC50; 3.34 ± 0.09, 14.00 ± 0.14, and 22.96 ± 1.23 µg/ ml during incubation durations of 10, 20, and 40 min). It also demonstrated a selective anti-inflammatory action against COX-2 rather than COX-1. Moreover, BMEPS exhibited antioxidant capabilities as free radical and oxygen reactive species (ROS) scavenger, metal chelator, reductant agent, and lipid peroxidation suppressor. These activities are due to the distinct chemical composition. The findings of this study indicate that BMEPS could be considered as promising anti-disease Alzheimer's (AD) material in an in-vitro model, which qualifies it for advanced in-vivo studies in the discovery of alternative Alzheimer's treatment.

Micellar eco-friendly HPLC method for simultaneous analysis of ternary combination of aspirin, atorvastatin and ramipril: application to content uniformity testing.

BACKGROUND: Cardiovascular disease medications such as aspirin (ASP), statins like atorvastatin (ATR), and blood pressure-lowering drugs including ACE inhibitors like ramipril (RAM) have been included in the World Health Organization (WHO) Essential Medicines List (EML) for many years. Therefore, there is a strong demand to develop a simple, rapid, and sensitive analytical method that can detect and quantitate the ternary mixture of these analytes in pharmaceutical preparations in a short run time. Lately, the analytical community focused on eliminating or reducing hazardous chemicals and solvents usage. RESULTS: A green, fast, selective, and cost-effective micellar HPLC method was established and validated for the concurrent determination of ternary combination of ASP, ATR, and RAM in the pure form and pharmaceutical preparations. Resolution of the three drugs was achieved by using a monolithic column and a micellar mobile phase consists of 0.3% triethylamine (TEA) in 90: 10 an aqueous solution of 0.12 M sodium dodecyl sulfate (SDS): n-propanol, (v/v). The pH was adjusted to 2.5 using orthophosphoric acid and a flow rate of 1.5 mL/min. was applied. To ensure method reproducibility, Valsartan (VAL) was utilized as an internal standard (IS). The UV detection of the studied drugs was performed at 210 nm. Good linearity for the three drugs was obtained over the concentration ranges of 1.0-200.0 mg/mL, 0.5-200.0 mg/mL, and 5.0-100.0 mg/mL with correlation coefficients of 0.9998,0.9999 and 0.9999 for ASP, ATR, and RAM respectively. The method sensitivity was revealed by the relatively small values of limits of detection (LOD) (0.19, 0.13 and 0.30 mg/mL) and limits of quantitation (LOQ) (0.63, 0.44 and 0.99 mg/mL) for ASP, ATR, and RAM, respectively. The retention times of ASP, ATR and RAM were 1.50, 2.3 and 4.3 min., respectively. CONCLUSIONS: The suggested technique was employed for the analysis of the three drugs in their prepared tablets maintaining the recommended pharmaceutical ratio without any interference from excipients. The method was further extended to content uniformity testing of RAM. The results were validated according to international council for harmonisation (ICH) guidelines.

Investigation of eco-friendly fluorescence quenching probes for assessment of acemetacin using silver nanoparticles and acriflavine reagent.

The non-steroidal anti-inflammatory medication acemetacin was assessed via two straightforward green spectrofluorimetric techniques. The quenching-dependent derivatizing spectrofluorimetric reactions are the master point of this study. Acriflavine-based method (Method I) depends on forming an ion association complex between acriflavine and the drug in a ratio of 1:1, decreasing the former's fluorescence intensity. Acriflavine or Ag NP's intensity-related quenching action goes linearly with the acemetacin concentration in the 2.0-20.0 µg/mL and 1.0-16.0 µg/mL ranges, respectively. The second quenching mechanism depends on using the silver nanoparticles (Ag NP's) as a fluorescence probe (Method II); Ag NP's were prepared from reducing silver nitrate using sodium borohydride. Both methods could be applied to determine pure and pharmaceutical dosage forms of acemetacin. The methods proved valid according to the international conference on harmonization (ICH) guidelines. In addition to this, this work has been estimated under green criteria assessment tools. There is no significant difference between the proposed and the comparison methods after the statistical interpretation.

Multicomponent spectrophotometric determination of a ternary mixture of widely-prescribed cardiovascular drugs by four different methods.

Four accurate, green, uncomplicated, and fast spectrophotometric procedures were established for the purpose of resolving as well as quantifying a ternary combination prescribed for cardiovascular patients, such as aspirin, atorvastatin, and ramipril. Method (A) is based on the first derivative zero-crossing spectrophotometry for the determination of aspirin and atorvastatin at 247.4 nm and 302.6 nm, respectively. Ramipril was determined using the second derivative at 211 nm. Method (B) depends on the ratio spectra first derivative (RDS) where the absorption spectrum of the ternary combination was divided by the spectrum of one of the analytes. When treated similarly, the concentrations of the other two analytes were measured using their corresponding calibration graphs. For the determination of ASP and RAM, ATR was used as a divisor with a concentration of 26 µg/mL, and the RDS values at 272.0 and 225.8 nm, respectively, were plotted against the ASP and RAM concentrations. Using 40 µg/mL ASP as a divisor, ATR was analyzed, and the RDS values at 295 nm were plotted versus the ATR concentration. Method (C) is based on the double divisor-ratio spectra derivative technique. In this technique, the derivative of the ratio spectrum is computed by dividing the absorption spectra of the studied combination by the standard spectrum of abinary combination of two of the three analytes being studied. The concentrations of the three analytes in the mixture were assayed by determining the absorbance either at the positive or the negative amplitude. For the determination of ASP, ATR, and RAM, the wavelengths used were 244, 295, and 220 nm, respectively. Method (D) was a hybrid double divisor-ratio spectra technique based on convolving the double divisor-ratio spectra with trigonometric Fourier functions. The magnitudes of the Fourier function coefficients at either maximum or minimum points were correlated to the concentration of each drug in the mixture. The specificity of the suggested methods was tested by analyzing synthetic laboratory-prepared combinations and laboratory-made tablets. Furthermore, the accuracy and precision were ensured by statistically comparing the obtained results with those obtained from comparison method using Bartlett's Test for Equality of Variances and ANOVA test.

Study of exopolysaccharide produced by Streptomyces rochie strain OF1 and its effect as ameliorative on osteoarthritis in rats via inhibiting TNF-α/COX2 pathway.

BACKGROUND: Carbohydrates are known as the main natural products of life activities. RESULTS: Streptomyces rochie strain OF1 isolated from a mangrove tree produced exopolysaccharide S5 (EPSS5) (14.2 gl-1) containing uronic acid 21.98% sulfate content of 11.65 mg/ml, and a viscosity of 1.35 mm2/s. while total hexose amine content was 24.72%. The high performance liquid chromatography (HPLC) analysis of mono sugars revealed that EPS was composed of manouronic acid, glucuronic acid, xylose, and fructose at a molar ratio of 1.0:0.5:1.0:2.0, respectively. It showed that the whole antioxidant activity was 92.06%. It showed antibacterial activity against Staphylococcus aureus, and E. coli, MRSA and Klebsiella pneumoniae. But, EPSS5 displayed low antifungal activity against Candida albicans. While no antifungal activity has been detected against Aspergillus niger. EPSS5 has antibiofilm action that is noticeable toward S. aureus with an inhibition ratio of biofilm up to 50%. Effect of EPS on serum levels of TNF-α and COX2 by 2 fold and 1.9 fold of EPS reduced serum levels of Tumor necrosis factor-α (TNF-α) by 38%, 12%, 49%, and Cyclooxygenase-2 (COX2) by 61%, 34%, and 62%, respectively. By affected of EPSS5 on arthritis in rats stimulated by carrageenan. CONCLUSIONS: Administration of EPS ameliorated carrageen-induced elevation in inflammatory mediators; TNF-α/COX and suppressed the expressions of metalloproteinase 9 (MMP9) by 68%, 86%, and 75% correspondingly in comparison to the group of carrageenans. Then again, therapy involving a high dose only reduced MMP9 level by 57%, compared to free drug suggesting that EPSS5 is a good inhibitor of the MMP9, as it brought MMP9 back to normal levels via the signaling pathway.

Insights into the spectrofluorometric determination of the neuromuscular blocker mivacurium chloride.

Fluorescence spectroscopy is gaining interest in the analysis and quantitative determination of different drugs. This study was carried out to investigate the fluorometric properties of the short-acting muscle relaxant mivacurium in its pure form, injection, and human plasma. It is nondepolarizing skeletal muscle relaxant for intravenous (IV) administration. Mivacurium shows a strong native fluorescence in methanol at 317 nm after excitation at 230 nm (Method I). The critical parameters that may influence the fluorescence of this drug were carefully studied. A linear response between concentration and fluorescence was constructed over the concentration range: 20.0 to 400.0 ng/mL with determination coefficient (r2) equal to 0.9998. Additionally, the correlation coefficient of the linear relationship (r) was found to be 0.9999 with a slope = 2.196 and intercept = -16.61. Limits of quantitation and detection were calculated mathematically to be 17.45 and 5.75 ng/mL respectively. Further estimation of mivacurium in spiked human plasma was performed by construction of specific calibration curve and the obtained correlation coefficient was 0.9948. Moreover, the ability to determine mivacurium in the presence of commonly co-administered drugs were investigated including propofol and thiopental. Method II includes the determination of MVC in the presence of propofol utilizing the first derivative synchronous fluorescence spectroscopy. The results of method II indicated acceptable percentage recoveries from 98.88 to 100.75 %. Statistical evaluation of the results revealed satisfactory accuracy and precision.

Rising trends in Caesarean section in 6 Egyptian governorates.

Background: Caesarean section (CS) is a life-saving operation when vaginal delivery is risky to the mother or baby. However, if not medically indicated or performed under suboptimal conditions, it can be harmful and resource-intensive. Aims: To estimate the prevalence of CS in 6 Egyptian governorates and identify possible risk factors (including demographic, social and healthcare services factors) stratified according to geographical areas. Methods: We used secondary data collected from a large survey to investigate the sociodemographic and health indicators of 6 purposefully selected Egyptian governorates with suboptimal health indicators: 3 from Upper Egypt (Sohag, Assiut and Menia) and 3 from Lower Egypt (Sharkia, Beheira and Ismailia). The survey data were gathered using an interview questionnaire that targeted household members. Results: The CS rate was estimated at 55.1% for the 3 years preceding the study, and the highest rate was 67.8% in Behira and the lowest was 49.0% in Assiut. In most governorates, the CS rate was higher in rural than in urban areas, but the difference was not significant. High CS rates were significantly related to higher social class and lower number of children (≤ 3). Conclusion: In the governorates investigated, CS was performed more often, with higher rates than those reported in the 2015 Egypt Health Issue Survey. The adoption of protocols for elective CS should be enforced with a more multisectoral effort. Pregnant women should be well informed of the risks associated with CS and its medical indications.

Insights on the Quantitative Concurrent Fluorescence-Based Analysis of Anti-COVID-19 Drugs Remdesivir and Favipiravir.

We hereby introduce a sensitive fast straightforward spectrofluorometric method for the estimation of remdesivir and favipiravir. The two drugs are prescribed in some regimens to treat COVID-19 pandemic disease, which is caused by SARS-CoV-2. The method is based on the first derivative synchronous spectrofluorimetry approach for the measurement of remdesivir and favipiravir. This was accomplished at 251 nm and 335 nm respectively using the first derivative order at delta lambda of 140 nm. A linear response with a correlation coefficient 0.9994 was achieved between the concentration and the derivative amplitudes in the ranges of 20.0-100.0 ng ml-1 and 40.0-100.0 ng ml-1 for remdesivir and favipiravir, respectively. The methods were validated for different parameters as stated by the pharmacopeial rules and were applied successfully for estimation of the studied drugs in their synthetic mixtures and in spiked human plasma samples. No significant difference was observed between the proposed and comparison methods as revealed from the analysis of data.

Correlates and reproductive consequences of consanguinity in six Egyptian governorates.

This study aimed to explore some correlates and potential reproductive consequences of consanguinity. We analysed data for 8515 ever-married women aged 15-49 derived from a household survey conducted in 2017 in six governorates. The prevalence of consanguineous marriage was 35.9%. The odds (OR (95%CI)) of consanguinity were higher in rural southern governorates (3.68 (3.03-4.46)), with less than secondary education (1.55 (1.42-1.7)), with unemployment (1.74(1.48-2.04)) and in the lowest wealth quintile (3.09 (2.66-3.6)). After adjusting for residence, education, wealth, age at marriage and the number of children; the OR (95%CI) for spontaneous abortion and still births with consanguinity were 1.31 (1.09-1.59) and 1.63 (1.18-2.25) respectively. Consanguinity remains highly prevalent in Egypt especially in rural southern governorates. Women empowerment in terms of attaining higher education and employment may reduce the problem. Consanguinity appears to be associated with adverse reproductive outcomes including spontaneous abortion and still birth.

Green quantitative spectrofluorometric analysis of rupatadine and montelukast at nanogram scale using direct and synchronous techniques.

Two green-sensitive spectrofluorometric methods were investigated for assay of rupatadine (RUP) [method I] and its binary mixture with montelukast (MKT) [method II]. Method I depends on measuring native fluorescence of RUP in the presence of 0.10 M H2SO4 and 0.10%w/v sodium dodecyl sulfate at 455 nm after excitation at 277 nm. The range of the first method was 0.20-2.00 µg ml-1 with detection and quantitation limits of 59.00 and 179.00 ng ml-1, respectively. Method II depends on the first derivative synchronous spectrofluorometry. The derivative intensities were measured for the two drugs in an aqueous solution containing Mcllvaine's buffer pH 2.60 at fixed Δλ of 140 nm. Each drug was estimated at zero-contribution of the other. The intensity was measured at 261 and 371 nm for RUP and MKT, respectively. The method was linear over 0.10-4.00 and 0.20-1.60 µg ml-1 with limits of detection 31.00 and 66.00 ng ml-1 and limits of quantitation 94.00 and 200.00 ng ml-1 for RUP and MKT, respectively. The method was extended to determine this mixture in laboratory-prepared mixtures and combined tablets. Method validation was performed according to ICH guidelines. Statistical interpretation of data revealed good agreement with the comparison method. Method greenness was confirmed by applying three different assessment tools.

Synthesis, Molecular Docking and Biological Evaluation of Novel Flavone Derivatives as Potential Anticancer Agents Targeting Akt.

BACKGROUND: Flavonoids are naturally occurring compounds with versatile healthpromoting effects against various diseases. OBJECTIVE: This aim of this paper is to synthesize and evaluate the biological activity of novel flavone derivatives against cancer. METHODS: A new series of 2-hydroxy-α,ß-unsaturated ketones 2a-h, was synthesized via the reaction of N-substituted-indole-3-carboxaldehyde 1a-h with 2-hydroxy acetophenone in the presence of piperidine. The oxidative cyclization of 2a-h using hydrogen peroxide/KOH and/or dimethyl sulfoxide/I2 produced the corresponding 2-(N-substituted-1H-indol-3-yl)-3-hydroxy-4H-chromen- 4-ones 3a-h and 2-(N-substituted-1H-indol-3-yl)-4H-chromen-4-ones 4a-h, respectively. Antiproliferative activities for synthesized series were investigated against HCT-116 colon and MCF- 7 breast cancer cell lines. Molecular downstream effects were evaluated using RT-PCR. Moreover, molecular docking was carried out to pinpoint the binding mode of the most active compounds into the active site of Akt enzyme (PDB ID: 3QKK). RESULTS: All compounds exhibited an anti-proliferative activity range of 52-97% and 67.2-99% against HCT-116 and MCF-7, respectively. Compounds 3b, 3h, 3g and 4h had a minimal inhibitory effect on normal BJ1 cells indicating their safety profile. Compounds 3b and 4h, in particular, exhibited the most potent antiproliferative activity against HCT116 and MCF7, meanwhile compounds 3g, 3h and 4g showed potent to moderate activity. Compound 3b had IC50 of 78.3 µM and 53.9 µM against HCT-116 and MCF-7 respectively with comparable IC50 for doxorubicin of 65.1 µM and 45.02 µM. Compound 3b exhibited significant down-regulation for Akt and significant up-regulation of CAS9 and CDKN1genes in all tested cell lines. CONCLUSION: The synthesized flavone derivatives and particularly compound 3b exhibited promising anticancer activity through Akt inhibition.

Diverse bioactive metabolites from Penicillium sp. MMA derived from the red sea: structure identification and biological activity studies.

A soft coral-derived fungus Penicillium sp. among other isolates e high antibacterial, anti-yeast and cytotoxic activities. The fungus, Penicillium sp. MMA, isolated from Sarcphyton glaucoma, afforded nine diverse compounds (1-9). Their structures were identified by 1D and 2 D NMR and ESI-MS spectroscopic data as two alkaloids: veridicatol (1), aurantiomide C (2); one sesquiterpene, aspterric acid (3); two carboxylic acids, 3,4-dihydroxy-benzoic acid; (4) and linoleic acid (5); three steroids, ergosterol (6), ß-Sitosterol (7), ß-Sitosterol glucoside (8) along with the sphingolipid, cerebroside A (9). Biologically, the antimicrobial, antioxidant, in vitro cytotoxicity and antibiofilm activities were studied in comparison with the fungal extract. The in silico computational studies were implemented to predict drug and lead likeness properties for 1-4. The fungus was taxonomically characterized by morphological and molecular biology (18srRNA) approaches.

Quantitative assessment of the nature of noncovalent interactions in N-substituted-5-(adamantan-1-yl)-1,3,4-thiadiazole-2-amines: insights from crystallographic and QTAIM analysis.

Three adamantane-1,3,4-thiadiazole hybrid derivatives namely; N-ethyl-5-(adamantan-1-yl)-1,3,4-thiadiazole-2-amine I, N-(4-fluorophenyl)-5-(adamantan-1-yl)-1,3,4-thiadiazole-2-amine II and (4-bromophenyl)-5-(adamantan-1-yl)-N-1,3,4-thiadiazole-2-amine III, have been synthesized and crystal structures have been determined at low temperature. The structures revealed that the orientation of the amino group is different in non-halogenated structures. Intra- and intermolecular interactions were characterized on the basis of the quantum theory of atoms-in-molecules (QTAIM) approach. Intermolecular interaction energies for different molecular pairs have been obtained using the PIXEL method. Hirshfeld surface analysis and 2D-fingerprint plots revealed that the relative contributions of different non-covalent interactions are comparable in compounds with halogen (Br and F) substitutions. Crystal structures of II and III show isostructural behaviour with 1D supramolecular constructs. In all three structures, the N-H⋯N hydrogen bond was found to be stronger among other noncovalent interactions. The H-H bonding showed a closed shell in nature and played significant roles in the stabilization of these crystal structures.

Assessment of lipophilicity of newly synthesized celecoxib analogues using reversed-phase HPLC.

BACKGROUND: Lipophilicity is a physicochemical property of an essential importance in medicinal chemistry; therefore, fast and reliable measurement of lipophilicity will affect greatly the drug discovery process. RESULTS: A series of N-benzenesulfonamide-1H-pyrazoles, oximes and hydrazones as celecoxib analogues was investigated with regard to their retention behavior using reversed-phase high performance liquid chromatography (RP-HPLC). The mobile phases employed for this study consist of a mixture of water and methanol in different proportions. In addition, the stationary phase utilized for this separation was C18 silanized silica gel and using 200 nm as a detection wavelength. The retention behavior of the investigated compounds was determined based on practical determination of log k at different concentrations of methanol (as an organic modifier) in the mobile phase ranging from 60 to 80%. It was observed that the retention of these compounds (expressed as log k) decreased in a linear manner with increasing the concentration of methanol. High correlation coefficients (more than 0.90 in most cases) were obtained for the relationship between the volume fraction of the organic solvent and the retention values represented as log k w. A comparative evaluation was carried out between chromatographically-obtained lipophilicity parameters (represented as lipophilicity chromatographic index log k w or isocratic chromatographic hydrophobicity index, φ 0) and the computationally calculated log P values (miLogP, ALOGP, ACD/Labs and ALOGPs). CONCLUSION: It was found that a good correlation exists between the experimental and computed log P values. In the future, these results can give a deep insight about the anti-inflammatory and analgesic activity of the newly synthesized compounds.