Anti-angiogenic activity of Morinda citrifolia extracts and its chemical constituents

Morinda citrifolia L. has been used for the treatment of a wide variety of diseases, including cancer. This study was undertaken to evaluate the anti-angiogenic effect of M. citrifolia fruits and leaves. Anti-angiogenic activity was evaluated in?vivo using the chick chorioallantoic membrane assay. Bioactivity-guided fractionation and isolation were performed to identify the active constituent, and high-performance liquid chromatography analysis was then used to quantify the amount of this active constituent in the active extracts and fraction. The methanol extracts of fruits and leaves of M. citrifolia and the subsequent chloroform fraction of the fruit methanolic extract were found to have potential anti-angiogenic activity and were more potent compared to suramin. Scopoletin was identified as one of the chemical constituents that may be partly responsible for the anti-angiogenic activity of M. citrifolia fruits. The present findings further support the use of M. citrifolia in cancer or other pathological conditions related to angiogenesis.     

Synthesis and preliminary investigations of the siRNA delivery potential of novel, single-chain rigid cationic carotenoid lipids

The success of nucleic acid delivery requires the development of safe and efficient delivery vectors that overcome cellular barriers for effective transport. Herein we describe the synthesis of a series of novel, single-chain rigid cationic carotenoid lipids and a study of their preliminary in vitro siRNA delivery effectiveness and cellular toxicity. The efficiency of siRNA delivery by the single-chain lipid series was compared with that of known cationic lipid vectors, 3β-[N-(N',N'-dimethylaminoethane)carbamoyl]-cholesterol (DC-Chol) and 1,2-dimyristoyl-sn-glyceryl-3-phosphoethanolamine (EPC) as positive controls. All cationic lipids (controls and single-chain lipids) were co-formulated into liposomes with the neutral co-lipid, 1,2-dioleolyl-sn-glycerol-3-phosphoethanolamine (DOPE). Cationic lipid-siRNA complexes of varying (+/-) molar charge ratios were formulated for delivery into HR5-CL11 cells. Of the five single-chain carotenoid lipids investigated, lipids 1, 2, 3 and 5 displayed significant knockdown efficiency with HR5-CL11 cells. In addition, lipid 1 exhibited the lowest levels of cytotoxicity with cell viability greater than 80% at all (+/-) molar charge ratios studied. This novel, single-chain rigid carotenoid-based cationic lipid represents a new class of transfection vector with excellent cell tolerance, accompanied with encouraging siRNA delivery efficiency.     

Modular and stereoselective formal synthesis of MeBmt, an unusual amino acid constituent of cyclosporin A

A convergent, flexible and stereoselective formal synthesis of MeBmt, the nonproteinogenic amino acid constituent of cyclosporin A is disclosed. The sulfinyl moiety has been exploited as the internal nucleophile to stereo- and regioselectively functionalize an allylic carbamate.     

Identification,control strategies,and analytical approaches for the determination of potential genotoxic impurities in pharmaceuticals: A comprehensive review

Potential genotoxic impurities in pharmaceuticals at trace levels are of increasing concern to both pharmaceutical industries and regulatory agencies due to their possibility for human carcinogenesis. Molecular functional groups that render starting materials and synthetic intermediates as reactive building blocks for small molecules may also be responsible for their genotoxicity. Determination of these genotoxic impurities at trace levels requires highly sensitive and selective analytical methodologies, which poses tremendous challenges on analytical communities in pharmaceutical research and development. Experimental guidance for the analytical determination of some important classes of genotoxic impurities is still unavailable in the literature. Therefore, the present review explores the structural alerts of commonly encountered potential genotoxic impurities, draft guidance of various regulatory authorities in order to control the level of impurities in drug substances and to assess their toxicity. This review also describes the analytical considerations for the determination of potential genotoxic impurities at trace levels and finally few case studies are also discussed for the determination of some important classes of potential genotoxic impurities. It is the authors’ intention to provide a complete strategy that helps analytical scientists for the analysis of such potential genotoxic impurities in pharmaceuticals.     

Capillary gas chromatographic analysis of pyrrolidinedithiocarbamate metal chelates

Pyrrolidinedithiocarbamate (PDTC) chelates of Zn(II), Cu(II), Ni(II), Co(III), Fe(III), Mn(II), Cr(III), and VO(II) were analysed by capillary GC on a DB-1701 column (30 m x 0.25 mm id) with flame ionisation detection (FID). Linear calibrations were attained within "1-30 microg/mL" for Ni(II), Fe(III), Mn(II), Cr(III), Cu(II), and VO(II), and within "2-50 microg/mL" for Co(III) and Zn(II). The limits of detection were in the "150-500 ng/mL" range, corresponding to 15-50 pg amounts reaching the FID system. The optimised method was applied to the determination of Cu(II) and Ni(II) in coins, and that of Zn(II), Cu(II), Ni(II), Fe(III), Mn(II), Cr(III), and VO(II) in pharmaceutical preparations with relative standard deviations within 1.1-5.2%. The results obtained are in good agreement with sewage water samples and the declared values for the pharmaceutical formulations, or with the results of AAS of metal contents in coins, pharmaceutical preparations, and sewage water samples.     

Bis­(O,O′‐di‐p‐tolyldithiophosphato‐S,S′)(1,10‐phenanthroline‐N,N′)nickel(II)

The title coordination complex, [Ni(C₁₄H₁₄O₂PS₂)₂(C₁₂H₈N₂)] or [Ni(pMePh‐dtp)₂(phen)] (phen is 1,10‐phenanthroline; dtp is di­aryl­di­thio­phosphate), has a non‐crystallographic twofold axis of symmetry through the Ni atom and the phen moiety. Two O,O‐di‐p‐tolyl­di­thio­phosphate (dtp) ions act as bidentate ligands. The central metal atom is coordinated by four S atoms from two dtp groups and two N atoms from the phen ligand. The title compound displays distorted octahedral geometry around the central Ni atom.     

Complexation of palladium cyanide with imidazolidine-2-thione and its derivatives

Summary Pd(CN)₂ reacts with imidazolidine-2-thione (Imt), 1,3-diazinane-2-thione(Diaz), 1,3-diazipnane-2-thione (Diap) and their derivatives to yield complexes of stoichiometry [PdL₂(CN)₂] or [PdL(CN)₂] (L = Imt, Diaz or Diap and L = Imt having N-Me, Et or Pr substituents), which were characterized by elemental analysis, i.r., ¹H and ¹³C n.m.r. spectroscopy. Both mono- and bis ligand complexes are thought to be square planar with the monoligand binding to metal via sulphur (bridging) and the bis ligand via the monodentate thione group. The ¹³C enriched Pd(¹³CN)₂ complex was prepared and the ¹³C n.m.r. recorded. The C-2 resonance of ¹³C n.m.r. of Imt, Diaz or Diap complexes of the copper(I), silver(I), gold(I) and palladium(II) were compared.     

Functional Properties and Molecular Degradation of Schizostachyum Brachycladum Bamboo Cellulose Nanofibre in PLA-Chitosan Bionanocomposites

The degradation and mechanical properties of potential polymeric materials used for green manufacturing are significant determinants. In this study, cellulose nanofibre was prepared from Schizostachyum brachycladum bamboo and used as reinforcement in the PLA/chitosan matrix using melt extrusion and compression moulding method. The cellulose nanofibre(CNF) was isolated using supercritical carbon dioxide and high-pressure homogenisation. The isolated CNF was characterised with transmission electron microscopy (TEM), FT-IR, zeta potential and particle size analysis. The mechanical, physical, and degradation properties of the resulting biocomposite were studied with moisture content, density, thickness swelling, tensile, flexural, scanning electron microscopy, thermogravimetry, and biodegradability analysis. The TEM, FT-IR, and particle size results showed successful isolation of cellulose nanofibre using this method. The result showed that the physical, mechanical, and degradation properties of PLA/chitosan/CNF biocomposite were significantly enhanced with cellulose nanofibre. The density, thickness swelling, and moisture content increased with the addition of CNF. Also, tensile strength and modulus; flexural strength and modulus increased; while the elongation reduced. The carbon residue from the thermal degradation and the glass transition temperature of the PLA/chitosan/CNF biocomposite was observed to increase with the addition of CNF. The result showed that the biocomposite has potential for green and sustainable industrial application.     

Microwave Irradiation and Glutamic Acid-Assisted Phytotreatment of Tannery and Surgical Industrial Wastewater by Sorghum

We investigated how different doses of microwave irradiation (MR) affect seed germination in Sorghum, including the level of remediation against textile and surgical wastewater (WW) by modulating biochemical and morpho-physiological mechanisms under glutamic acid (GA) application. The experiment was conducted to determine the impact of foliar-applied GA on Sorghum under wastewater conditions. Plants were treated with or without microwave irradiation (30 s, 2.45 GHz), GA (5 and 10 mM), and wastewater (0, 25, 50, and 100). Growth and photosynthetic pigments were significantly decreased in plants only treated with various concentrations of WW. GA significantly improved the plant growth characteristics both in MR-treated and -untreated plants compared with respective controls. HMs stress increased electrolyte leakage (EL), hydrogen peroxide (H₂O₂), and malondialdehyde (MDA) content; however, the GA chelation significantly improved the antioxidant enzymes activities such as ascorbate oxidase (APX), superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) both in MR-treated and -untreated plants under WW stress compared with respective controls. The results suggested that the MR-treated plants accumulate higher levels of HMs under GA addition in comparison to the WW-only-treated and MR-untreated plants. The maximum increase in Cd accumulation was observed in the range of 14–629% in the roots, 15–2964% in the stems, and 26–4020% in the leaves; the accumulation of Cu was 18–2757% in the roots, 15–4506% in the stems, and 23–4605% in the leaves; and the accumulation of Pb was 13–4122% in the roots, 21–3588% in the stems, and 21–4990% in the leaves under 10 mM GA and MR-treated plants. These findings confirmed that MR-treated sorghum plants had a higher capacity for HMs uptake under GA and could be used as a potential candidate for wastewater treatment.     

Xanthene-Based Nitric Oxide-Responsive Nanosensor for Photoacoustic Imaging in the SWIR Window

Shortwave infrared (SWIR) dyes are characterized by their ability to absorb light from 900 to 1400 nm, which is ideal for deep tissue imaging owing to minimized light scattering and interference from endogenous pigments. An approach to access such molecules is to tune the photophysical properties of known near-infrared dyes. Herein, we report the development of a series of easily accessible (three steps) SWIR xanthene dyes based on a dibenzazepine donor conjugated to thiophene ( SCR-1 ), thienothiophene ( SCR-2 ), or bithiophene ( SCR-3 ). We leverage the fact that SCR-1 undergoes a bathochromic shift when aggregated for in vivo studies by developing a ratiometric nanoparticle for NO ( rNP-NO ), which we employed to successfully visualize pathological levels of nitric oxide in a drug-induced liver injury model via deep tissue SWIR photoacoustic (PA) imaging. Our work demonstrates how easily this dye series can be utilized as a component in nanosensor designs for imaging studies.