Application of the Pictet-Spengler reaction to aryl amine-based substrates having pyrimidine as a π-nucleophile: synthesis of pyrimidoquinolines with structural analogy to benzonaphthyridines present in alkaloids

Synthesis of pyrimidine annulated quinolines, structurally analogous to biologically active benzonaphthyridines present in alkaloids, has been described. Our synthetic strategy is based on the modified Pictet-Spengler reaction involving substrates comprising deactivated pyrimidine ring as the nucleophilic partner whereas aryl amine originating from the C-4 of the pyrimidine ring served as the source for electrophilic partner. The resulting substrates 5-7 with diversity at 2- and 6-position after condensation with a variety of aldehydes underwent 6-endo cyclization to furnish pyrimido[5,4-c]quinolines 14 in good yields. However, attempts to further extend this strategy on new structurally analogous substrate involving the pyridine ring as nucleophilic partner failed, thus limiting the scope of the reaction.     

Polymerizing Insulin with Photocleavable Linkers to Make Light‐Sensitive Macropolymer Depot Materials

The use of light‐sensitive polymers for the release of therapeutics is an important approach allowing the timing and amount of the release to be controlled precisely. The use of light has been pioneered to control insulin release from a dermal photoactivated depot, or PAD. One of the main impediments to the use of light‐sensitive polymers in this context is the density of the materials: The large majority of the material is the carrier polymer, with the minority being the therapeutic. In this work, the feasibility of using insulin itself as a monomer in the polymerization process is demonstrated. Insulin modified with either one or two light cleavable azide groups is polymerized with a tridentate alkyne‐bridging monomer using a click reaction. The resulting material called a “macropolymer” is ≈85% insulin, is insoluble in aqueous solvent, and releases native, soluble insulin upon irradiation.

     

Thermal kinetics involved during the solid-state synthesis of Cr2AlC MAX phase

Journal of Thermal Analysis and Calorimetry - The formation of nanolaminated Cr2AlC MAX phase by using solid-state synthesis route has been investigated through thermal analysis technique. The...     

Iodine-catalysed regioselective synthesis of β-hydroxysulfides

A metal-free, and environment benign iodine-catalysed protocol has been developed for the regioselective synthesis of β-hydroxysulfides in good to excellent yields from easily accessible styrenes and thiophenols. The reaction involves single step CS and CO bonds construction.     

Evaluation of Raman spectroscopy for prediction of antitumor response to silibinin and its nanoparticulates in DMBA‐induced oral carcinogenesis

Raman spectroscopy is a vibrational spectroscopic technique that can be used to monitor the therapeutic efficacy of anticancer drugs during carcinogenesis in a non‐invasive and label‐free manner. The present study aims to investigate the biochemical changes exerted upon free silibinin (SIL) and its nanoparticulate (SILNPs) treatment against 7,12‐dimethylbenz[a]anthracene (DMBA)‐induced oral carcinogenesis in the fingerprint region of 1800–500 cm⁻¹ using HE‐785 Raman spectrometer. Raman spectra differed significantly between the control and tumor tissues, with tumor tissues characterized by increased intensities of vibrational bands such as nucleic acids, phenylalanine and tryptophan and a lower percentage of lipids when compared to the control tissues. Further, oral administration of free SIL and SILNPs significantly increased lipids and decreased the levels of tryptophan, phenylalanine and nucleic acid contents. Overall, the treatment of nanoparticulate SIL was found to be a more potent antitumor effect than free SIL in preventing the formation of tumor and also brought back the several Raman bands to a normal range in the buccal mucosa of hamsters during DMBA‐induced oral carcinogenesis. In addition, the detailed secondary structure of proteins in the control and experimental groups is also presented. Furthermore, the diagnostic algorithms based on principal component linear discriminant analysis (PC‐LDA) achieved an overall sensitivity of 94–100% and specificity of 76–100%. These results further demonstrate that Raman spectroscopy associated with PC‐LDA diagnostic algorithms could be a valuable tool for rapid and sensitive detection of specific biomolecular changes at the molecular level in response to anticancer drug. Copyright © 2015 John Wiley & Sons, Ltd.     

Chemical Composition and Biological Activities of Hedychium coccineum Buch.-Ham. ex Sm. Essential Oils from Kumaun Hills of Uttarakhand

Hedychium coccineum Buch. Ham. ex Sm. is a perennial rhizomatous herb belonging to the family Zingiberaceae. The aim of the present study was to compare the chemical composition and biological activities of H. coccineum rhizome essential oil (HCCRO) and H. coccineum aerial part essential oil (HCCAO). The plant material was subjected to hydro-distillation using Clevenger’s apparatus in order to obtain volatile oil and analyzed for its chemical constituents using GC-MS. The comparative study of the rhizome and aerial part essential oils of H. coccineum displayed that (E)-nerolidol (15.9%), bornyl acetate (13.95%), davanone B (10.9%), spathulenol (8.9%), and 1, 8-cineol (8.5%) contributed majorly to the HCCRO, while 7-hydroxyfarnesen (15.5%), α-farnesene (11.1%), α-pinene (10.9%), spathulenol (7.7%), and β-pinene (6.8%) were present as major constituents in the HCCAO. Both the essential oils were studied for their biological activities, such as nematicidal, insecticidal, herbicidal, antifungal, and antibacterial activities. The essential oils exhibited significant nematicidal activity against Meloidogyne incognita, insecticidal activity against Spodoptera litura, and moderate herbicidal activity against R. raphanistrum sub sp. sativus, and good antifungal activity against Fusarium oxysporum and Curvularialunata. Essential oils were also tested for antibacterial activity against Staphylococcus aureus and Salmonella enterica serotype Typhi. Both oils showed good to moderate activity against the tested pathogens. The significant nematicidal, insecticidal, herbicidal, antifungal, and antibacterial activities of both the essential oils might be helpful for the development of environmentally friendly pesticides that could be an alternative to synthetic pesticides in the future.     

Formulation and evaluation of gel containing nanostructured lipid carriers of tretinoin–Epi-β-CD binary complex for topical delivery

The objective of present research work was to formulate and evaluate topical gel containing tretinoin–cyclodextrin (CD) binary complex loaded into nanostructured lipid carriers (NLCs). Use of cyclodextrin and nanolipid carrier together in a system produced a synergistic effect by increasing the drug release and skin permeation, thus improving the overall therapeutic effect. Two different cyclodextrins i.e. β-CD and its water soluble polymeric derivative epichlorohydrin-β-cyclodextrin (EPI-β-CD) were used to obtain binary inclusion complex of drug-cyclodextrin (D-CD) systems by two different techniques (kneading and co-evaporation). The prepared solid complexes were characterized by FTIR, DSC, XRD etc. and the best system was selected for loading into nanolipid carriers. NLC comprising glyceryl mono stearate (GMS) and oleic acid were obtained by slightly modified emulsification evaporation method. Four different formulations of NLCs were suitability characterized for particle size, zeta potential, entrapment efficiency, drug loading and drug release. EPI-β-CD was found to be more effective than β-CD in enhancing solubility and dissolution properties of tretinoin. The most effective NLC formulation was incorporated into carbopol hydrogel which showed better permeation properties than that of the reference gel (0.1%).     

Individual and simultaneous voltammetric determination of ascorbic acid,uric acid and folic acid by using a glassy carbon electrode modified with gold nanoparticles linked to bentonite via cysteine groups

A voltammetric sensor for both the individual and the simultaneous determination of ascorbic acid (AA), uric acid (UA) and folic acid (FA) is described. It is based on a glassy carbon electrode (GCE) that was modified with bentonite (Bnt) that was first functionalized with cysteine (Cys) to which gold nanoparticles were linked. The resulting material (referred to as Au-Cys-Bnt) and the other materials were characterized by UV-vis spectroscopy, powder X-ray diffraction (XRD), scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy (XPS), energy dispersive X-ray analysis and electrochemical methods. The XRD peak positions of bentonite and Cys-functionalized bentonite prove the incorporation of Cys into bentonite. The XPS spectrum of Au-Cys-Bnt confirms the interaction of gold nanoparticles with the thiol group of Cys. The modified GCE displays high electrocatalytic activity for the oxidation of AA, UA and FA, typically at 0.19, 0.41, and 0.73 V (vs. SCE), respectively. Differential pulse voltammetric data show a linear response that covers the 1 μM to 25 mM concentration range for AA, the 1 to 200 μM concentration range for UA, and two linear ranges for FA, one from 5 to 100 μM and one from 100 μM to 1.5 mM. The sensor was applied to the determination of AA, UA and FA in (spiked) multi-vitamin syrup, bird serum and milk samples.

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Graphical abstract Schematic of a sensor for simultaneous and individual electrochemical determination of ascorbic, uric, and folic acids in real samples. The sensor consists of a glassy carbon electrode that was modified with a nanocomposite prepared from bentonite that was first functionalized with cysteine to which gold nanoparticles were linked.

     

Efficient synthesis of acridinediones in aqueous media

An efficient synthesis of acridinediones in two steps have been achieved using water as a reaction media without chromatographic purification. First step involves the reaction of dimedone with ammonium acetate to yield enaminone in water which on further reaction with various aldehydes yields acridinedione in aqueous media. The reaction merits the use of water as solvent, no additive catalyst and provides high yield of products with good purity.     

Coordination Adducts of Niobium(V) and Tantalum(V) Azide M(N3)5 (M=Nb,Ta) with Nitrogen Donor Ligands and their Self‐Ionization

Several new donor–acceptor adducts of niobium and tantalum pentaazide with N‐donor ligands have been prepared from the pentafluorides by fluoride–azide exchange with Me₃SiN₃ in the presence of the corresponding donor ligand. With 2,2′‐bipyridine and 1,10‐phenanthroline, the self‐ionization products [MF₄(2,2′‐bipy)₂]⁺[M(N₃)₆]^?, [M(N₃)₄(2,2′‐bipy)₂]⁺[M(N₃)₆]^? and [M(N₃)₄(1,10‐phen)₂]⁺[M(N₃)₆]^? were obtained. With the donor ligands 3,3′‐bipyridine and 4,4′‐bipyridine the neutral pentaazide adducts (M(N₃)₅)₂?L (M=Nb, Ta; L=3,3′‐bipy, 4,4′‐bipy) were formed.