Shift to Pseudomonic acid B production in P. fluorescens NCIMB10586 by mutation of mupirocin tailoring genes mupO, mupU, mupV, and macpE

Mupirocin, a polyketide-derived antibiotic from Pseudomonas fluorescens NCIMB10586, is a mixture of pseudomonic acids (PA) that target isoleucyl-tRNA synthase. The mup gene cluster encodes both type I polyketide synthases and monofunctional enzymes that should play a role during the conversion of the product of the polyketide synthase into the active antibiotic (tailoring). By in-frame deletion analysis of selected tailoring open-reading frames we show that mupQ, mupS, mupT, and mupW are essential for mupirocin production, whereas mupO, mupU, mupV, and macpE are essential for production of PA-A but not PA-B. Therefore, PA-B is not simply produced by hydroxylation of PA-A but is either a precursor of PA-A or a shunt product. In the mupW mutant, a new metabolite lacking the tetrahydropyran ring is produced, implicating mupW in oxidation of the 16-methyl group.     

L-proline catalyzed asymmetric transfer aldol reaction between diacetone alcohol and aldehydes

We demonstrate for the first time, L-proline as a chiral catalyst for transfer aldol reaction between aldehydes and diacetone alcohol.     

Triiron and Triruthenium Carbonyl Clusters Bearing Bridging Long Chain Diphosphine and Capping Chalcogenido Ligands

Treatment of Ru₃(CO)₁₂ with dpphSe₂ (dpph = 1,6-bis(diphenylphosphino)hexane) in refluxing toluene in the presence of Me₃NO afforded two new compounds, Ru₃(CO)₇(-CO)(₃-Se)(-dpph) (1) and Ru₃(CO)₇(₃-Se)₂(-dpph) (2). A similar reaction of Ru₃(CO)₁₂ with dpppeSe₂ (dpppe = 1,5-bis(diphenylphosphino)pentane) gave exclusively Ru₃(CO)₇(₃-Se)₂(-dpppe) (3). Treatment of Ru₃(CO)₁₂ with dpphS₂ and dpppeS₂ at 110°C in the presence of Me₃NO afforded Ru₃(CO)₇(₃-S)₂(-dpph) (4) and Ru₃(CO)₇(₃-S)₂(-dpppe) (5), respectively. Reactions of Fe₃(CO)₁₂ with dpphSe₂ and dpppeSe₂, under identical conditions, afforded Fe₃(CO)₇(₃-Se)₂(-dpph) (6) and Fe₃(CO)₇(₃-Se)₂(-dpppe) (7), respectively. Compounds 1–7 were characterized spectroscopically and the molecular structures of compounds 1–4 were determined by single crystal X-ray crystallography. The core of 1 contains an equilateral triangle of ruthenium atoms with one capping selenium, one bridging dpph, one doubly bridging carbonyl and seven terminal carbonyl ligands. Complexes 2–4 have a square-pyramidal structure with two metal and two chalcogenide atoms alternating in the basal plane and the third metal atom at the apex of the pyramid, and belong to the family of well-known nido clusters with seven skeletal electron pairs.     

Formulation and In Vitro Evaluation of Sustained Release Microspheres of Diltiazem Hydrochloride Prepared by Emulsification-Internal Gelation Method

The present work describes the formulation of alginate microspheres containing diltiazem hydrochloride by the emulsification-internal gelation method with the use of barium carbonate as a cross-linking agent. The effect of various factors (the concentration of alginate and barium chloride) on the drug loading efficiency and in vitro release were investigated. Fourier transform infrared microscopy (FTIR) and differential scanninig calorimetry (DSC) analysis confirmed the absence of any drug polymer interaction. X-ray diffraction (XRD) pattern showed that there is a decrease crystallinity of the drug. The in vitro drug release profile could be altered significantly by changing various processing parameters to give a controlled release of drug from microcapsules. The stability studies of drug-loaded microcapsules showed that the drug was stable at different storage conditions.     

Exogenous Sodium Nitroprusside Mitigates Salt Stress in Lentil (Lens culinaris Medik.) by Affecting the Growth,Yield, and Biochemical Properties

Soil salinity disrupts the physiological and biochemical processes of crop plants and ultimately leads to compromising future food security. Sodium nitroprusside (SNP), a contributor to nitric oxide (NO), holds the potential to alleviate abiotic stress effects and boost tolerance in plants, whereas less information is available on its role in salt-stressed lentils. We examined the effect of exogenously applied SNP on salt-stressed lentil plants by monitoring plant growth and yield-related attributes, biochemistry of enzymes (superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD)) amassing of leaf malondialdehyde (MDA) and hydrogen peroxide (H₂O₂). Salinity stress was induced by NaCl application at concentrations of 50 mM (moderate salinity) and 100 mM (severe salinity), while it was alleviated by SNP application at concentrations of 50 µM and 100 µM. Salinity stress severely inhibited the length of roots and shoots, the relative water content, and the chlorophyll content of the leaves, the number of branches, pods, seeds, seed yield, and biomass per plant. In addition, MDA, H₂O₂ as well as SOD, CAT, and POD activities were increased with increasing salinity levels. Plants supplemented with SNP (100 µM) showed a significant improvement in the growth- and yield-contributing parameters, especially in plants grown under moderate salinity (50 mM NaCl). Essentially, the application of 100 µM SNP remained effective to rescue lentil plants under moderate salinity by regulating plant growth and biochemical pathways. Thus, the exogenous application of SNP could be developed as a useful strategy for improving the performance of lentil plants in salinity-prone environments.     

Synthesis of linseed oil based biodegradable homo and copolymers: role as multifunctional greener additives in lube oil

Abstract

Homopolymer of linseed oil and its four copolymers with styrene, 1-decene, isodecyl acrylate and octyl acrylate, respectively, have been synthesized in this present context. The prepared polymers are characterized by NMR and FTIR spectroscopy. The molecular weights have been measured by gel permeation chromatography. Their effectiveness as pour point depressant (PPD), viscosity index improver (VII) and their shear stability in terms of permanent shear stability index have been evaluated in lube oil. The copolymers acted as better PPDs than the homopolymer whereas the homopolymer of linseed oil excelled as VII. Further it was observed that all the prepared polymers were stable enough under severe mechanical shear.     

Convergent synthesis of carbonic anhydrase inhibiting bi-heterocyclic benzamides: Structure–activity relationship and mechanistic explorations through enzyme inhibition,kinetics, and computational studies

By using a convergent methodology, a novel series of N-arylated 4-yl-benzamides containing a bi-heterocyclic thiazole–triazole core was synthesized, and the structures of these hybrid molecules, 9a–k , were corroborated through spectral analyses. The in vitro studies of these multifunctional molecules demonstrated their potent carbonic anhydrase inhibition relative to the standard used. The kinetics mechanism was exposed by Lineweaver–Burk plots, which revealed that 9j inhibited carbonic anhydrase non-competitively by forming an enzyme-inhibitor complex. The inhibition constants K_i calculated from Dixon plots for this compound was 1.2 μM. The computational study was also persuasive with the experimental results, and these molecules disclosed good results of all scoring functions and interactions, which suggested a good binding to carbonic anhydrase. So, it was predicted from the inferred results that these molecules might be considered as promising medicinal scaffolds for various diseases related to the uncontrolled production of this enzyme.     

In-vitro drug–drug interaction studies of diltiazem with floroquinolones

Diltiazem is an established cardiovascular drug mainly used for the management of hypertension specifically for the angina pectoris. Fluoroquinolones are widely prescribed against the treatment of severe infections. In vitro relations of diltiazem with fluoroquinolones (ciprofloxacin, levofloxacin, norfloxacin, and ofloxacin) were examined using spectrophotometric and separation techniques, i.e., RP-HPLC. Diltiazem’s availabilities were observed to be predisposed highly in the presence of fluoroquinolones. To investigate the mechanism of interaction in a variety of dissolution environments, i.e., simulating body environments with regard to pH on these interactions has been studied. Moreover, complex of diltiazem–fluoroquinolones were prepared and elucidated through IR spectroscopy and confirmed by computational molecular modeling.