Natural Isatin Derivatives Against Black Fungus: In Silico Studies.

During this coronavirus pandemic, when a lot of people are already severely afflicted with SARS-CoV-19, the dispersion of black fungus is making it worse, especially in the Indian subcontinent. Considering this situation, the idea for an in silico study to identify the potential inhibitor against black fungal infection is envisioned and computational analysis has been conducted with isatin derivatives that exhibit considerable antifungal activity. Through this in silico study, several pharmacokinetics properties like absorption, distribution, metabolism, excretion, and toxicity (ADMET) are estimated for various derivatives. Lipinski rules have been used to observe the drug likeliness property, and to study the electronic properties of the molecules, quantum mechanism was analyzed using the density functional theory (DFT). After applying molecular docking of the isatin derivatives with sterol 14-alpha demethylase enzyme of black fungus, a far higher docking affinity score has been observed for the isatin sulfonamide-34 (derivative 1) than the standard fluconazole. Lastly, molecular dynamic (MD) simulation has been performed for 100 ns to examine the stability of the proposed drug complex by estimating Root Mean Square Deviation (RMSD), Radius of gyration (Rg), Solvent accessible surface area (SASA), Root Mean Square Fluctuation (RMSF), as well as hydrogen bond. Listed ligands have precisely satisfied every pharmacokinetics requirement for a qualified drug candidate and they are non-toxic, non-carcinogenic, and have high stability. This natural molecule known as isatin derivative 1 has shown the potential of being a drug for fungal treatment. However, the impact of the chemicals on living cells requires more investigation and research.

High index core flat fiber surface plasmon resonance bio-sensor.

Due to tremendous design flexibility and ease of light control capability, the photonic crystal fiber offers efficient, flexible, and miniaturized plasmonic biosensors with attractive features. In this work, a high index (GeO2 doped silica) core flat fiber is proposed and analyzed for RI sensing ranging from 1.53 to 1.60. A rectangular analyte channel is created on top of a flat fiber to better handle the liquid analyte. To introduce the plasmonic effect, TiO2 and gold are deposited to the analyte channel. The sensing performance is carried out for two operating wavelengths, as two peaks are obtained for each analyte. The second operating wavelength shows better sensing performance than the first one. However, the proposed sensor offers average wavelength sensitivity of 5000 nm/RIU with a sensor resolution of 2×10-05 RIU. In addition, the proposed sensor shows identical linearity, which is quite rare in prior sensors. Moreover, the proposed flat sensor provides outstanding detection accuracy of 0.01nm-1, detection limit of 79.28 nm, signal to noise ratio of -4.1497dB, and figure of merit of 50RIU-1. Owing to outstanding sensing performance and a unique detection range, this sensor can be effectively used in biological and organic analyte sensing applications.

Analyses of (1-chloroethenyl)oxirane headspace and hemoglobin N-valine adducts in erythrocytes indicate selective detoxification of (1-chloroethenyl)oxirane enantiomers.

Chloroprene (2-chloro-1,3-butadiene, CAS 126-99-8, CP) is a colorless volatile liquid used in manufacture of polychloroprene, a synthetic rubber polymer. National Toxicology Program inhalation studies of CP in rats and mice gave clear evidence of carcinogenic activity. CP is metabolized by CYP2E1 to electrophilic epoxides, including R- and S-(1-chloroethenyl)oxirane (CEO), which form adducts with nucleic acids and other nucleophiles including glutathione and hemoglobin. As detection of these epoxide metabolites in vivo is technically challenging, measurements of CEO-Hb adducts may provide biomarkers of exposure to bioactivated metabolites of CP. The present studies involved exposure of C57BL/6 mouse erythrocytes (RBC) in vitro to pure enantiomers of CEO. Headspace analysis of CEO using Cyclodex-B capillary GC/MS with selected ion monitoring enabled separation, specific detection, and quantification of CEO enantiomers as reactions proceeded in vitro with RBC. These analyses indicated that R-CEO was much more persistent when incubated in vitro with RBC, while S-CEO disappeared rapidly. After periods of exposure of RBC to various concentrations of R- or S-CEO, erythrocytes were lysed and globin isolated. Covalent adducts, formed by reaction of CEO with N-terminal valine in Hb, were analyzed following Edman cleavage and trimethylsilylation. SIM-GC/MS analyses using a 5%-phenyl-dimethylsiloxane capillary column enabled quantification of CEO-Hb adducts. These analyses produced two chromatographic peaks of CEO-valine adduct derivatives, which were tentatively identified from mass spectra, reaction, and abundance data to be 1-(3-chloro-2-trimethylsilyloxybut-3-en-1-yl)-5-isopropyl-3-phenyl-2-thiohydantoin and 1-[2-chloro-1-(trimethylsilyloxymethyl)prop-2-en-1-yl]-5-isopropyl-3-phenyl-2-thiohydantoin. Analyses quantified significantly greater levels of adducts formed from R-CEO than from S-CEO. Studies involving pretreatment of RBC with glutathione-depleting diethyl maleate diminished the selective detoxification of S-CEO, and suggest enantiomeric selectivity of mouse glutathione-S-transferase as a mechanism of differential detoxification of CEO enantiomers. These results indicate more rapid detoxification of S-CEO by mouse RBC in vitro, while R-CEO may persist to react with cellular nucleophiles.

Determination of tobacco specific hemoglobin adducts in smoking mothers and new born babies by mass spectrometry.

Biological markers for assessment of exposure to a variety of environmental carcinogens has been widely applied in both basic as well as clinical research. Exposure to tobacco smoke presents an ideal environment with which to develop, characterize, and refine biological markers, especially of those carcinogens found in tobacco. In the present study, a sensitive gas chromatography/mass spectrometry (GC/MS) method was developed to measure nitrosamine- hemoglobin adducts (HPB-Hb (4-Hydroxy-3-pyridinyl-1-butanone) at trace levels in red blood cells of both African-American and Caucasian smoking and nonsmoking mothers and their infants. Gas chromatographic and mass spectrometric methods with chemical ionization (CI) of methane reagent gas in both positive and negative ion mode as well as electron ionization (EI) were studied to determine differences in sensitivity of detection among the various ionization methods. Detection limits using both positive and negative chemical ionization modes were found to be 30 femtomoles of HPB, whereas detection using electron impact modes yielded a detection limit of 80 femtomoles of HBP. Comparative derivatization of HPB was performed using O-bis(Trimethylsilyl)-trifluoroacetamide (BSTFA) and 2, 3, 4, 5, 6-Pentafluorobenzoylchloride (PFBC). Both Negative CI and Positive CI modes of analysis were compared to the more widely accepted EI modes of mass spectrometric analysis.

One-step SFE-plus-C(18) selective extraction of low-polarity compounds, with lipid removal, from smoked fish and bovine milk.

Co-extraction of lipid materials is the major source of interference in determinations of low-polarity compounds in many biological matrixes. "SFE-plus-C(18)", a recently developed supercritical fluid extraction method employing C(18) adsorbent in the extraction chamber, can enable selective extraction of low-polarity compounds in lipid-rich biological matrixes without a cleanup step. This study reports the application of the SFE-plus-C(18) method to the quantification of: 1. polycyclic aromatic hydrocarbons (PAH) in commercially purchased smoked fish; and 2. anti-cancer agents cyclophosphamide (CP) and suberoylanilide hydroxamic acid (SAHA) spiked into homogenized whole bovine milk. Over the course of SFE-plus-C(18)extraction, indigenous lipids are preferentially retained on the C(18) adsorbent. Compared with the conventional method, only 8-15% of the lipids in the smoked fish sample, and only 6-18% of the lipids in the milk sample, were co-extracted by SFE-plus-C(18). This reduction in the quantity of background lipids significantly improved chromatographic separations, retarded deterioration of the column, and dramatically improved the ability to quantify PAH present at trace levels in smoked fish by GC-MS. Using the SFE-plus-C(18) method, ten targeted PAH were detected in the range 9.5-13.5 ng g(-1) in the smoked fish sample. Compared with these levels, PAH extractions by use of conventional SFE gave values that were lower by 38-86%. Recoveries of CP and SAHA spiked into milk were close to 100% in both SFE-plus-C(18)and conventional SFE, where the lipid background during the chromatographic elution of CP and SAHA was not so severe.