Structural hybridization of three aminoglycoside antibiotics yields a potent broad-spectrum bactericide that eludes bacterial resistance enzymes

MedChemComm ◽  
2016 ◽  
Vol 7 (1) ◽  
pp. 170-176 ◽  
Author(s):  
Juan Pablo Maianti ◽  
Stephen Hanessian

Systematically blending structural features from obsolete aminoglycosides gleaned from X-ray co-crystal models rendered a promising antibiotic inert to enzymatic modification.

Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 439
Author(s):  
Christopher G. Bunick ◽  
Jonette Keri ◽  
S. Ken Tanaka ◽  
Nika Furey ◽  
Giovanni Damiani ◽  
...  

Prolonged broad-spectrum antibiotic use is more likely to induce bacterial resistance and dysbiosis of skin and gut microflora. First and second-generation tetracycline-class antibiotics have similar broad-spectrum antibacterial activity. Targeted tetracycline-class antibiotics are needed to limit antimicrobial resistance and improve patient outcomes. Sarecycline is a narrow-spectrum, third-generation tetracycline-class antibiotic Food and Drug Administration (FDA)-approved for treating moderate-to-severe acne. In vitro studies demonstrated activity against clinically relevant Gram-positive bacteria but reduced activity against Gram-negative bacteria. Recent studies have provided insight into how the structure of sarecycline, with a unique C7 moiety, interacts with bacterial ribosomes to block translation and prevent antibiotic resistance. Sarecycline reduces Staphylococcus aureus DNA and protein synthesis with limited effects on RNA, lipid, and bacterial wall synthesis. In agreement with in vitro data, sarecycline demonstrated narrower-spectrum in vivo activity in murine models of infection, exhibiting activity against S. aureus, but reduced efficacy against Escherichia coli compared to doxycycline and minocycline. In a murine neutropenic thigh wound infection model, sarecycline was as effective as doxycycline against S. aureus. The anti-inflammatory activity of sarecycline was comparable to doxycycline and minocycline in a rat paw edema model. Here, we review the antibacterial mechanisms of sarecycline and report results of in vivo studies of infection and inflammation.


2014 ◽  
Vol 783-786 ◽  
pp. 1426-1431
Author(s):  
Wang Ryeol Kim ◽  
Min Chul Kwon ◽  
Jung Hoon Lee ◽  
Uoo Chang Jung ◽  
Won Sub Chung

TiAlSiN coatings were deposited on WC-Co metal by using a cathodic arc ion deposition method of cylindrical cathode. We used Ti / Al (50 / 50 at.%) arc target and silicon sputter target. The influence of the nitrogen pressure, TiAl cathode arc current, bias voltage, and deposition temperature on the mechanical and the structural properties of the films were investigated. The structural features of the films were investigation in detail using X-ray diffraction. And coatings were characterized by means of FE-SEM, nanoindentation, Scratch tester, Tribology tester, XRD and XPS. The hardness of the film reached 43 GPa at the cathode arc current of 230 A and decreased with a further increase of the arc current. And the adhesion of the film reached 34 N. The results showed that the TiAlSiN coating exhibited an excellent mechanical properties which application for tools and molds.


2008 ◽  
Vol 1069 ◽  
Author(s):  
Ryoji Kosugi ◽  
Toyokazu Sakata ◽  
Yuuki Sakuma ◽  
Tsutomu Yatsuo ◽  
Hirofumi Matsuhata ◽  
...  

ABSTRACTIn practical use of the SiC power MOSFETs, further reduction of the channel resistance, high stability under harsh environments, and also, high product yield of large area devices are indispensable. Pn diodes with large chip area have been already reported with high fabrication yield, however, there is few reports in terms of the power MOSFETs. To clarify the difference between the simple pn diodes and power MOSFETs, we have fabricated four pn-type junction TEGs having the different structural features. Those pn junctions are close to the similar structure of DIMOS (Double-implanted MOS) step-by-step from the simple pn diodes. We have surveyed the V-I characteristics dependence on each structural features over the 2inch wafer. Before their fabrication, we formed grid patterns with numbering over the 2inch wafer, then performed the synchrotron x-ray topography observation. This enables the direct comparison the electrical and spectrographic characteristics of each pn junctions with the fingerprints of defects.Four structural features from TypeA to TypeD are as follows. TypeA is the most simple structure as same as the standard pn diodes formed by Al+ ion implantation (I/I), except that the Al+ I/I condition conforms to that of the p-well I/I in the DIMOS. The JTE structure was used for the edge termination on all junctions. While the TypeA consists of one p-type region, TypeB and TypeC consists of a lot of p-wells. The difference of Type B and C is a difference of the oxide between the adjacent p-wells. The oxide of TypeB consists of the thick field oxide, while that of TypeC consists of the thermal oxide corresponding to the gate oxide in the DIMOS. In the TypeD structure, n+ region corresponding to the source in the DIMOS was added by the P+ I/I. The TypeD is the same structure of the DIMOS, except that the gate and source contacts are shorted. The V-I measurements of the pn junctions are performed using the KEITHLEY 237 voltage source meters with semi-auto probe machine. An active area of the fabricated pn junctions TEGs are 150um2 and 1mm2. Concentration and thickness of the drift layer are 1e16cm−3 and 10um, respectively.In order to compare the V-I characteristics of fabricated pn junctions with their defects information that obtained from x-ray topography measurements directly, the grid patterns are formed before the fabrication. The grid patterns were formed over the 2inch wafer by the SiC etching. The synchrotron x-ray topography measurements are carried out at the Beam-Line 15C in Photon-Factory in High-Energy-Accelerator-Research-Organization. Three diffraction conditions, g=11-28, -1-128, and 1-108, are chosen in grazing-incidence geometry (improved Berg-Barrett method).In the presentation, the V-I characteristics mapping on the 2inch wafer for each pn junctions, and the comparison of V-I characteristics with x-ray topography will be reported.


2021 ◽  
Vol 17 ◽  
Author(s):  
Hummera Rafique ◽  
Aamer Saeed ◽  
Muhammad Naseem ◽  
Tauqeer Riaz ◽  
Fouzia Perveen ◽  
...  

Background: Heterocyclic compounds display versatile biological applications, so the aim of this paper was to prepare biologically important heterocycles with enhanced bacterial resistance and to evaluate for their various structural features that are responsible for their biological properties. Objective: The objective was to synthesize bacterial resistance compounds with enhanced antibacterial properties. Method: Ester moiety containing thiazole ring was converted into its hydrazide derivatives. These heterocyclic derivatives were cyclized into another ring oxadiazole; hence a hybrid ring system of two biologically active rings was prepared. Result: All the synthesized compounds were characterized by spectroscopic techniques and were screened for their antibacterial potential; they possess significant antibacterial activities. Conclusion: New hybrid heterocyclic ring systems were synthesized by cyclization of hydrazide derivatives by adopting two step strategy in good yields. All the synthesized compounds were evaluated for their antioxidant activities; they showed moderate to significant activities. QSAR and Molecular docking studies were performed to determine the mode of interaction. Experimental and computational data is in accordance with the determined antibacterial activities.


2018 ◽  
Vol 46 (6) ◽  
pp. 1431-1447 ◽  
Author(s):  
Tobias Tandrup ◽  
Kristian E. H. Frandsen ◽  
Katja S. Johansen ◽  
Jean-Guy Berrin ◽  
Leila Lo Leggio

Lytic polysaccharide monooxygenases (LPMOs) are copper enzymes discovered within the last 10 years. By degrading recalcitrant substrates oxidatively, these enzymes are major contributors to the recycling of carbon in nature and are being used in the biorefinery industry. Recently, two new families of LPMOs have been defined and structurally characterized, AA14 and AA15, sharing many of previously found structural features. However, unlike most LPMOs to date, AA14 degrades xylan in the context of complex substrates, while AA15 is particularly interesting because they expand the presence of LPMOs from the predominantly microbial to the animal kingdom. The first two neutron crystallography structures have been determined, which, together with high-resolution room temperature X-ray structures, have putatively identified oxygen species at or near the active site of LPMOs. Many recent computational and experimental studies have also investigated the mechanism of action and substrate-binding mode of LPMOs. Perhaps, the most significant recent advance is the increasing structural and biochemical evidence, suggesting that LPMOs follow different mechanistic pathways with different substrates, co-substrates and reductants, by behaving as monooxygenases or peroxygenases with molecular oxygen or hydrogen peroxide as a co-substrate, respectively.


1990 ◽  
Vol 45 (7) ◽  
pp. 1084-1090 ◽  
Author(s):  
Klaus Praefcke ◽  
Bernd Kohne ◽  
Andreas Eckert ◽  
Joachim Hempel

Six S,S-dialkyl acetals 2a-f of inosose (1), tripodal in structure, have been synthesized, characterized and investigated by optical microscopy and differential scanning calorimetry (d.s.c.). The four S,S-acetals 2c-f with sufficiently long alkyl chains are thermotropic liquid crystalline; 2 e and 2 f are even dithermomesomorphic. Each of these four inosose derivatives 2c-f exhibits monotropically a most likely cubic mesophase (MI); in addition 2e and 2f show enantiotropically a hexagonal mesophase (Hx) with a non-covalent, supramolecular H-bridge architecture. Whereas the nature of the optically isotropic mesophase MI needs further clarification the stable high temperature mesophase Hx of 2 e and 2 f has been established by a miscibility test using a sugar S,S-dialkyl acetal also tripodal in structure and with a Hx phase proved by X-ray diffraction, but in contrast to 2 with an acyclic hydrophilic part. Similarities of structural features between the Hx-phases of 2e and 2f as well as of other thermotropic and lyotropic liquid crystal systems are discussed briefly.


ISRN Ceramics ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Bahman Nasiri-Tabrizi ◽  
Abbas Fahami

Fluorapatite-zinc oxide (FAp-ZnO) composite nanopowders were successfully prepared via mechanochemical process. Characterization of the products was carried out by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR) analysis, energy dispersive X-ray spectroscopy (EDX), and field-emission scanning electron microscopy (FE-SEM) techniques. Results revealed that in the absence of ZnO which produced by hydrothermal method, the single-phase FAp had high-crystalline structure with appropriate morphological features. Furthermore, after 5 h of milling in the presence of 5 wt.% ZnO, FAp-5 wt.% ZnO, composite nanopowders with no impurity phase was obtained. Structural studies illustrated that the milling up to 5 h was not accompanied by a remarkable change in the structural features. Moreover, the gained composite powders presented an average crystallite size of about 40 nm for FAp. The FE-SEM observations indicated that the experimental outcome had a cluster-like structure which consisted of several small particles. Finally, results propose a new approach to prepare commercial amounts of novel FAp-based composite nanopowders with high quality and suitable structural and morphological features.


Author(s):  
E. A. Shaporova ◽  
A. A. Zhukova ◽  
A. K. Baev ◽  
A. Yu. Sidorenko

The article is devoted to the study of the nature and number of acid-base centers on the surface of chromium(III) oxide obtained by precipitation from an aqueous nitrate solution. The curve of the distribution of the number of acidbase centers of the samples is plotted depending on the indicator of the ionization constant of indicators. It was determined that the main Lewis centers make the main contribution to the acidity of the samples; there are also Bronsted centers of different acidity. A comparative analysis of the structural features of the surface of oxides of chromium, zinc and binary systems Cr (III)–Zn (II) was carried out according to the results of X-ray phase analysis of oxides and thermolysis of the corresponding hydroxides. Based on this, the possibility of obtaining nanosized catalysts based on oxide-hydroxide systems of chromium with a number of 3d-metals obtained in the process of polynuclear hydroxocomplexation is predicted.


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