Use of chemically modified thermoresponsive copolymers for the detection of C-reactive protein

Fluorescence intensity of N-isopropylacrylamide-glycidyl methacrylate (NIPAAm-GMA) copolymer conjugated with fluoreseinamine isomer1 was found to decrease considerably in the presence of NIPAAm-GMA copolymer containing O-phosphorylethanolamine (PEA), the specific ligand of C-reactive protein (CRP). The decrease in the emission intensity was reasoned due to the quenching of the fluorescence through the interaction of the polymer chains. The emission intensity was, however, found to increase rapidly when CRP was added in to the solution containing the polymers. The intensity of fluorescence emission was increased by five-fold in the presence of CRP as low as 20 ng mL⁻¹. Albumin, the major blood protein, did not show any interference in the emission. The presence of a low molecular protein, cytochrome c, on the fluorescence spectra was also studied and this protein also found not have any influence in binding of CRP onto the ligand indicating that other proteins irrespective of their molecular weights did not influence the measurement. A definite correlation was found between the concentration of CRP and the fluorescence intensity. The method appears to be very sensitive and easy to perform. The study reflects, for the first time, the scope of using copolymeric combinations for the measurement of CRP without the use of antibody.     

An ab initio and matrix isolation infrared study of the 1:1 C2H2–CHCl3 adduct

The details of weak C–Hπ interactions that control several inter and intramolecular structures have been studied experimentally and theoretically for the 1:1 C₂H₂–CHCl₃ adduct. The adduct was generated by depositing acetylene and chloroform in an argon matrix and a 1:1 complex of these species was identified using infrared spectroscopy. Formation of the adduct was evidenced by shifts in the vibrational frequencies compared to C₂H₂ and CHCl₃ species. The molecular structure, vibrational frequencies and stabilization energies of the complex were predicted at the MP2/6-311+G(d,p) and B3LYP/6-311+G(d,p) levels. Both the computational and experimental data indicate that the C₂H₂–CHCl₃ complex has a weak hydrogen bond involving a C–Hπ interaction, where the C₂H₂ acts as a proton acceptor and the CHCl₃ as the proton donor. In addition, there also appears to be a secondary interaction between one of the chlorine atoms of CHCl₃ and a hydrogen in C₂H₂. The combination of the C–Hπ interaction and the secondary ClH interaction determines the structure and the energetics of the C₂H₂–CHCl₃ complex. In addition to the vibrational assignments for the C₂H₂–CHCl₃ complex we have also observed and assigned features owing to the proton accepting C₂H₂ submolecule in the acetylene dimer.     

Design of Novel Coumarin Derivatives as NUDT5 Antagonists That Act by Restricting ATP Synthesis in Breast Cancer Cells

Breast cancer, a heterogeneous disease, is among the most frequently diagnosed diseases and is the second leading cause of death due to cancer among women after lung cancer. Phytoactives (plant-based derivatives) and their derivatives are safer than synthetic compounds in combating chemoresistance. In the current work, a template-based design of the coumarin derivative was designed to target the ADP-sugar pyrophosphatase protein. The novel coumarin derivative (2R)-2-((S)-sec-butyl)-5-oxo-4-(2-oxochroman-4-yl)-2,5-dihydro-1H-pyrrol-3-olate was designed. Molecular docking studies provided a docking score of −6.574 kcal/mol and an MM-GBSA value of −29.15 kcal/mol. Molecular dynamics simulation studies were carried out for 500 ns, providing better insights into the interaction. An RMSD change of 2.4 Å proved that there was a stable interaction and that there was no conformational change induced to the receptor. Metadynamics studies were performed to calculate the unbinding energy of the principal compound with NUDT5, which was found to be −75.171 kcal/mol. In vitro validation via a cytotoxicity assay (MTT assay) of the principal compound was carried out with quercetin as a positive control in the MCF7 cell line and with an IC₅₀ value of 55.57 (+/−) 0.7 μg/mL. This work promoted the research of novel natural derivatives to discover their anticancer activity.     

Alkaloids and flavonoids of Argemone mexicana

A new protopine alkaloid, protomexicine and a new isoflavonoid, mexitin, together with 8-methoxydihydrosanguinarine, 13-oxoprotopine, rutin and quercetrin have been isolated from the aerial part of the methanolic extract of Argemone mexicana. The structures of these compounds have been established by various spectral data. The structure of protomexicine was further confirmed by heteronuclear multiple bond correlation experiment. Protomexicine and mexitin are new compounds, and other compounds are first reported from A. mexicana and genus Argemone.     

Development of stability-indicating assay method and liquid chromatography-quadrupole-time-of-flight mass spectrometry-based structural characterization of the forced degradation products of alpelisib

The US Food and Drug Administration and the European Medicines Agency approved alpelisib in 2019 for the treatment of metastatic breast cancer. A thorough literature review revealed that a stability-indicating analytical method (SIAM) is not available for the quantification of alpelisib and its degradation products (DPs). In this study, per the comprehensive stress study recommended by the International Council for Harmonisation (ICH), alpelisib was exposed to hydrolysis, oxidation, photolysis, and thermal stress. Degradation of the drug was observed under hydrolysis, oxidative, and photolysis conditions, whereas the drug was stable under thermal stress condition. We developed a SIAM for the separation of alpelisib and its major DPs that were formed under different stress conditions. The validation of the developed method was performed per ICH Q2(R1) guidelines. Five DPs were identified and characterized. Structure elucidation of all DPs was performed with the modern characterization tool of liquid chromatography-quadrupole time-of-flight mass spectrometer (LC-Q-TOF-MS/MS). The degradation pathway of the drug and its mechanisms were outlined, and in silico toxicity prediction was performed using the ProTox-II tool.     

Regioselective Synthesis of 1,3,5-Trisubstituted Pyrazoles

Abstract

A new and a simple approach toward synthesis of 1,3,5-trisubstituted pyrazoles from chalcone arylhydrazones via oxidative cyclization has been achieved. 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone was successfully used as an oxidizing agent to give excellent yields of pyrazoles.     

An Unprecedented Synthesis of 3,3‐Disubstituted Isochroman‐1,4‐diones Using Nitrones as Oxygen Atom Donors

A one‐pot reaction of ninhydrin, N‐methyl‐C‐phenyl nitrone, and secondary amine leading to the unprecedented synthesis of 3,3‐disubstituted isochroman‐1,4‐diones is described here. In this reaction, nitrone acts as an oxygen atom donor producing an imine as a side product. The mild reaction conditions, the flexibility of the secondary amines that can be used, the novelty of the product, and the good yields are the highlights of this reaction.     

Quantitation of Eugenol,Cinnamaldehyde and Isoeugenol from Cinnamomum tamala Nees and Eberm. Leaf Powder and Cinnamomum zeylanicum Breyn Stem Bark Powder by LC

An LC method has been developed for the simultaneous quantitative determination of eugenol, cinnamaldehyde and isoeugenol from dried leaf powder of Cinnamomum tamala Nees & Eberm and stem bark powder of Cinnamomum zeylanicum Breyn. Linear responses for eugenol, cinnamaldehyde and isoeugenol were obtained over the concentration ranges of 0.20–2.50, 5.00–100.00 and 0.10–1.00 μg mL⁻¹, respectively.

     

Screening of silver nanoparticles containing carbonized yeast cells for adsorption of few long-lived active radionuclides

The present study involves the screening of silver nanoparticles containing carbonized yeast cells isolated from coconut cell sap for efficient adsorption of few long lived radionuclides like ¹³⁷Cs₅₅, ⁶⁰Co₂₇, ¹⁰⁶Ru₄₄, ²³⁹Pu₉₄ and ²⁴¹Am₉₅. Yeast cells containing silver nanoparticles produced through biological reduction were subjected to carbonization (400 °C for 1 h) at atmospheric conditions and their properties were analyzed using fourier transform infra-red spectroscopy, X-ray diffraction, scanning electron microscope attached with energy dispersive spectroscopy and transmission electron microscope. The average size of the silver nanoparticles present on the surface of the carbonized silver containing yeast cells (CSY) was 19 ± 9 nm. The carbonized control yeast cells without silver exposure (CCY) did not contain any particles on its surface. The efficiency of CSY and CCY towards the radionuclide adsorption was studied in batch mode at fixed contact time, concentration, and at its native pH. CSY was efficient in removal of ²³⁹Pu₉₄ (76.75%) and ¹⁰⁶Ru₄₄ (54.73%) whereas CCY showed efficient removal only for ²⁴¹Am₉₅ (62.89%). Both the adsorbents did not show any retention with respect to ⁶⁰Co₂₇ and ¹³⁷Cs₅₅. Based on the experimental data, decontamination factor and distribution coefficient (K _d) were calculated and, from the values, it was observed that these adsorbents have greater potential to adsorb radionuclides.