The Experts below are selected from a list of 126 Experts worldwide ranked by ideXlab platform
Nagendra N. Mishra - One of the best experts on this subject based on the ideXlab platform.
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Comparative Efficacies of Linezolid vs. Tedizolid in an Experimental Murine Model of Vancomycin-Resistant Enterococcal (VRE) Bacteremia
Frontiers in medicine, 2019Co-Authors: Wessam Abdelhady, Nagendra N. MishraAbstract:Tedizolid (TZD) is an Oxazolidinone Derivative which demonstrates bacteriostatic activity through inhibition of protein synthesis. We compared the efficacies of TZD and an earlier-generation Oxazolidinone, linezolid (LZD), in an experimental murine model of bacteremia caused by two VRE strains (one each E. faecium and E. faecalis). LZD exhibited significantly better efficacy in terms of reduced VRE blood and target tissue densities than TZD in this model.
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Data_Sheet_1_Comparative Efficacies of Linezolid vs. Tedizolid in an Experimental Murine Model of Vancomycin-Resistant Enterococcal (VRE) Bacteremia.docx
2019Co-Authors: Wessam Abdelhady, Nagendra N. MishraAbstract:Tedizolid (TZD) is an Oxazolidinone Derivative which demonstrates bacteriostatic activity through inhibition of protein synthesis. We compared the efficacies of TZD and an earlier-generation Oxazolidinone, linezolid (LZD), in an experimental murine model of bacteremia caused by two VRE strains (one each E. faecium and E. faecalis). LZD exhibited significantly better efficacy in terms of reduced VRE blood and target tissue densities than TZD in this model.
Wessam Abdelhady - One of the best experts on this subject based on the ideXlab platform.
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Comparative Efficacies of Linezolid vs. Tedizolid in an Experimental Murine Model of Vancomycin-Resistant Enterococcal (VRE) Bacteremia
Frontiers in medicine, 2019Co-Authors: Wessam Abdelhady, Nagendra N. MishraAbstract:Tedizolid (TZD) is an Oxazolidinone Derivative which demonstrates bacteriostatic activity through inhibition of protein synthesis. We compared the efficacies of TZD and an earlier-generation Oxazolidinone, linezolid (LZD), in an experimental murine model of bacteremia caused by two VRE strains (one each E. faecium and E. faecalis). LZD exhibited significantly better efficacy in terms of reduced VRE blood and target tissue densities than TZD in this model.
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Data_Sheet_1_Comparative Efficacies of Linezolid vs. Tedizolid in an Experimental Murine Model of Vancomycin-Resistant Enterococcal (VRE) Bacteremia.docx
2019Co-Authors: Wessam Abdelhady, Nagendra N. MishraAbstract:Tedizolid (TZD) is an Oxazolidinone Derivative which demonstrates bacteriostatic activity through inhibition of protein synthesis. We compared the efficacies of TZD and an earlier-generation Oxazolidinone, linezolid (LZD), in an experimental murine model of bacteremia caused by two VRE strains (one each E. faecium and E. faecalis). LZD exhibited significantly better efficacy in terms of reduced VRE blood and target tissue densities than TZD in this model.
Žinić Mladen - One of the best experts on this subject based on the ideXlab platform.
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Lariat ethers with pendant phenanthridine units. Synthesis and complexation of Na- and K-picrate.
'Croatian Chemical Society', 1999Co-Authors: Alihodžić Sulejman, Žinić MladenAbstract:Lariat ethers 12 and 13 with appended phenanthridine fluorophoric units have been prepared as potential fluorescent chemosensor molecules for alkaline metal salts possessing aromatic anions. The starting 8-ethyloxycarbonylamino-6-methylphenanthridine (1) was converted via 2, 3, 6 and 7 to N-(2-tosylethyl)-Derivatives 4 and 8 suitable for N-alkylations of diaza- and aza-18-crown-6. However, the alkylations failed, giving the 2-Oxazolidinone Derivative 5 formed by intramolecular cyclization of phenanthridine N-carbamate Derivatives 4 and 8 in basic conditions. The phenanthridine Derivative 10 having benzyl instead carbamate protection on 8-amino group successfully alkylated mono- and diaza-crown ethers, giving lariats 12 and 14. Subsequent removal of benzyl protection groups in acidic conditions gave lariats 13 and 15. Lariat 12 was found to form unique Na- and K-picrate complexes with the metal cation bound in the crown cavity and picrate anion intercalated between phenanthridine units
Mladen Žinić - One of the best experts on this subject based on the ideXlab platform.
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Lariat ethers with pendant phenanthridine units. Synthesis and complexation of Na- and K-picrate
Croatica Chemica Acta, 1999Co-Authors: Sulejman Alihodžić, Mladen ŽinićAbstract:Abstract: Lariat ethers 12 and 13 with appended phenanthridine fluorophoric units have been prepared as potential fluorescent chemosensor molecules for alkaline metal salts possessing aromatic anions. The starting 8-ethyloxycarbonylamino-6-methylphenanthridine was converted via 2, 3, 6 and 7 to N-(2-tosylethyl)-Derivatives 4 and 8 suitable for N-alkylations of diaza-and aza-18-crown-6. However the alkylations failed giving instead the 2-Oxazolidinone Derivative 5 formed by intramolecular cyclisation of phenanthridine N-carbamate Derivatives 4 and 8 in basic conditions. The phenanthridine Derivative 10 having benzyl instead carbamate protection on 8-amino group successfully alkylated mono- and diaza-crown ethers giving lariats 12 and 14. The subsequent removal of benzyl protection groups in acidic conditions gave lariats 13 and 15. Lariat 12 was found to form the unique Na and K-picrate complexes with the metal cation bound in the crown cavity and picrate anion intercalated between phenanthridine units.
Oludotun A Phillips - One of the best experts on this subject based on the ideXlab platform.
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a novel Oxazolidinone Derivative ph192 demonstrates anticonvulsant activity in vivo in rats and mice
European Journal of Pharmaceutical Sciences, 2019Co-Authors: Mohamed G Qaddoumi, Oludotun A Phillips, Samuel B KombianAbstract:Abstract The pharmacotherapeutic management of seizure disorders with currently available medications is not optimal due to side effects and failure of some patients to respond to all available medications. As such there is the need to develop new antiseizure drugs by looking at new chemical classes of compounds. We recently screened, in vitro, a new class of compounds, the Oxazolidinones, for actions in the brain that may indicate potential for antiseizure activity. A few compounds were identified with such a potential. Here we tested whether one of these lead compounds, PH192, will exhibit in vivo antiseizure activity using chemically- and electrically- induced seizures models in mice and rats. Out of 5 compounds tested, all of them had minimal neurotoxicological effects in mice, with PH192 being the best, with comparable efficacy (ED50) and toxicity (TD50) to only levetiracetam. Intraperitoneal (IP) pretreatment with PH192 produced a dose-dependent protection of mice from seizures induced using the 6 Hz stimulation protocol with an estimated ED50 of 34.5 mg/kg in mice and about 90 mg/kg in rats and a neurotoxic dose >500 mg/kg in mice, yielding a calculated neuro (protective) index of >14.7. When pretreated with 100 mg/kg PH192 for 30 min, about 75% of mice were protected from 6 Hz-induced seizures. When rats were pretreated for 30 min with PH192, 66.6% of rats were protected from seizures induced using the 6 Hz stimulation protocol while 83.3% were protected using the maximal electroshock (MES) stimulation protocol. Pentylenetetrazole (PTZ) injection at 50, and 100 mg/kg produced stage 5 seizures in all rats. Thirty minutes IP pretreatment of rats with 100 mg/kg PH192 protected 80% of rats from the PTZ-induced seizures, a level of protection similar to that obtained with a reference antiepileptic drug (AED) phenytoin (40 mg/kg), that is used clinically for the treatment of various seizure disorders. The results of these studies indicate that PH192 protects against both chemically- and electrically-induced seizures with little central nervous system side effects. This suggests that the Oxazolidinone pharmacophore has potential for discovering new antiepileptic drugs with possibly minimal central side effects.
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a validated uplc ms ms method for the analysis of linezolid and a novel Oxazolidinone Derivative ph027 in plasma and its application to tissue distribution study in rabbits
Journal of Chromatography B, 2017Co-Authors: Mohsen A Hedaya, Vidhya Thomas, Mohamed E Abdelhamid, Elijah O Kehinde, Oludotun A PhillipsAbstract:Abstract Objectives Linezolid is the first approved Oxazolidinone antibacterial agent, whereas PH027 is a novel compound of the same class that exhibits good in vitro antibacterial activity. The objective of this study was to develop an UPLC–MS/MS assay for the analysis of linezolid and PH027 in plasma and to apply the method for comparative pharmacokinetic and tissue distribution studies of both compounds. Method Plasma samples and calibrators were extracted with diethyl ether after addition of the internal standard solution. After evaporation of the ether layer, the residue was reconstituted in mobile phase and injected into UPLC–MS/MS. The mobile phase consisted of 2 mM ammonium acetate buffer solution and acetonitrile (70:30) at a flow rate of 0.2 ml/min. Separation was achieved using UPLC BEH C18 column, and quantitative determination of the analytes was performed using multiple-reaction monitoring (MRM) scanning mode. The method was validated by analyzing quality control tissue homogenate samples, and was applied to analyze tissue homogenate samples obtained following IV injections of linezolid and PH027 in rabbits. Results The developed UPLC–MS/MS method was linear in the concentration range of 50–5000 ng/ml. Validation of the method proved that the method's precision, selectivity and stability were all within the acceptable limits. Linezolid and PH027 concentrations were accurately determined in the quality control tissue homogenate samples, and analysis of samples obtained following IV administration of the two compounds showed that the tissue to plasma concentration ratio of PH027 was higher than that of linezolid probably due to its higher lipophilicity. Conclusions The developed UPLC–MS/MS method for the analysis of linezolid and PH027 in rabbit's plasma can accurately determine the concentrations of these compounds in different tissues.
