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Armando Rossello - One of the best experts on this subject based on the ideXlab platform.

  • synthesis and inhibitory activity towards human leukocyte elastase of new 7α methoxy and 7α chloro 2 acyloxymethyl cephem derivatives
    European Journal of Medicinal Chemistry, 2001
    Co-Authors: Alberto Balsamo, Daniela Gentili, Simona Rapposelli, Marco Macchia, Giovanni Cercignani, Elisabetta Orlandini, Annalina Lapucci, Armando Rossello
    Abstract:

    Some new cephem derivatives of types 4 and 5, viewed as analogues of type I esters in which the atomic sequence of the C-2 ester group is formally inverted, were synthesised and tested in vitro for their inhibitory activity towards human leukocyte elastase and porcine pancreatic elastase. An examination of the inhibition data obtained for the new type 4 and 5 derivatives, while exhibiting a considerable reduction in their activity against porcine pancreatic elastase, indicated that these compounds still maintain an appreciable inhibitory activity against human leukocyte elastase. On this basis the new type of C-2 substitution appears to contribute to the research of new, potentially interesting, cephalosporinic human leukocyte elastase inhibitors.

  • Synthesis and inhibitory activity towards human leukocyte elastase of new 7 alpha-methoxy and 7 alpha-chloro (2-acyloxymethyl) cephem derivatives
    'Elsevier BV', 2001
    Co-Authors: Alberto Balsamo, Daniela Gentili, Simona Rapposelli, Marco Macchia, Elisabetta Orlandini, Annalina Lapucci, Cercignani G, Armando Rossello
    Abstract:

    Some new cephem derivatives of types 4 and 5, viewed as analogues of type I esters in which the atomic sequence of the C-2 ester group is formally inverted, were synthesised and tested in vitro for their inhibitory activity towards human leukocyte elastase and porcine pancreatic elastase. An examination of the inhibition data obtained for the new type 4 and 5 derivatives, while exhibiting a considerable reduction in their activity against porcine pancreatic elastase, indicated that these compounds still maintain an appreciable inhibitory activity against human leukocyte elastase. On this basis the new type of C-2 substitution appears to contribute to the research of new, potentially interesting, cephalosporinic human leukocyte elastase inhibitors

Ettore Perrone - One of the best experts on this subject based on the ideXlab platform.

Paul Waikei Tsang - One of the best experts on this subject based on the ideXlab platform.

  • entrapment of a trigonopsis variabilis d amino acid oxidase variant f54y for oxidative deamination of cephalosporin c
    Engineering in Life Sciences, 2011
    Co-Authors: Kinsing Wong, Wingping Fong, Paul Waikei Tsang
    Abstract:

    Trigonopsis variabilisD-amino acid oxidase (TvDAAO) is an enzyme used in the industrial bioconversion of cephalosporin C (CPC) into 7-aminocephalosporanic acid, a crucial biosynthetic nucleus for a wide spectrum of semi-synthetic cephem antibiotics. Using homology modeling and site-directed mutagenesis, we have previously shown that the TvDAAO variant F54Y possesses improved catalytic activity and thermostability. To further explore its industrial application, the conditions for immobilization of the enzyme were examined in the present investigation. The results showed that entrapment in a calcium alginate (Ca-alginate) matrix using 2% alginate, 500 mM CaCl2, and 15 min stabilization appeared to be optimal for the immobilization of F54Y. The entrapped enzyme allowed complete CPC conversion. The entrapped enzyme also showed good operational stability and retained at least 90% of its original activity after 20 reaction cycles. To conclude, the entrapment of F54Y in Ca-alginate appeared to be a simple and efficient biocatalysis system with potential application in the antibiotics industry.

Akio Miyake - One of the best experts on this subject based on the ideXlab platform.

  • studies on anti mrsa parenteral cephalosporins i synthesis and antibacterial activity of 7β 2 5 amino l52 4 thiadiazol 3 yl 2 z hydroxyiminoacetamido 3 substituted imidazo 1 2 6 pyridazinium 1 yl methyl 3 cephem 4 carboxylates and related compounds
    The Journal of Antibiotics, 2000
    Co-Authors: Tomoyasu Ishikawa, Yuji Iizawa, Kenji Okonogi, Akio Miyake
    Abstract:

    In an effort to discover a novel cefozopran (CZOP) derivative having excellent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), we performed chemical modification of the alkoxyimino moiety and imidazo[1, 2-b]pyridazinium group of CZOP. Among the prepared compounds, the cyclopentyloxyimino derivative 7β-[2-(5-amino-1, 2, 4-thiadiazol-3-yl)-2(Z)-cyclopentyloxyiminoacetamido]-3-(3, 6-diaminoimidazo[1, 2-b]pyridazinium-l-yl)methyl-3-cephem-4-carboxylate (20g) showed the most potent anti-MRSA activity, reflecting its high affinity (IC50=1.6 μg/ml) for penicillin binding protein 2' (PBP2'), although its anti-MRSA activity was slightly inferior to that of vancomycin (VCM). In experimental systemic infection in mice, however, 20g showed activity comparable to that of VCM against MRSA. In addition, 20g showed activity similar or slightly inferior to that of CZOP against Pseudomonas aeruginosa both in vitro and in vivo. Considering its favorable antibacterial activity profile, 20g was considered to be the most promising CZOP derivative for further studies.

  • studies on anti mrsa parenteral cephalosporins iii synthesis and antibacterial activity of 7 beta 2 5 amino 1 2 4 thiadiazol 3 yl 2 z alkoxyiminoacetamido 3 e 2 1 alkylimidazo 1 2 b pyridazinium 6 yl thiovinyl 3 cephem 4 carboxylates and related comp
    The Journal of Antibiotics, 2000
    Co-Authors: Tomoyasu Ishikawa, Keiji Kamiyama, Yutaka Nakayama, Yuji Iizawa, Kenji Okonogi, Akio Miyake
    Abstract:

    In the course of our exploration for a novel cephalosporin derivative having excellent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), we modified the C-3 linked spacers of cephem derivatives bearing a l-methylimidazo[l, 2-b]pyridazinium-6-yl group at the C-3' position and 2-(5-amino-l, 2, 4-thiadiazol-3-yl)-2(Z)-cyclopentyloxyiminoacetyl group at the C-7 position. The optimal spacers were the (E)-2-vinyl and (E)-2-thiovinyl groups seen in 19a and 29aa, respectively. Their anti-MRSA activity was 16 to 32 times as potent as that of cefozopran (CZOP). Focusing on the (E)-2-vinyl and (E)-2-thiovinyl spacers, we further modified the alkoxyimino groups in the C-7 acyl moiety and the 1-alkylimidazo[l, 2-b]pyridazinium moieties at the C-3' position and investigated the structureactivity relationships (SAR) of the derivatives. Consequently, we selected 7β-[2-(5-aminol, 2, 4-thiadiazol-3-yl)-2(Z)-fluoromethoxyiminoacetamido]-3-[(E)-2-(l-methylimidazo[l, 2-b]pyridazinium-6-yl)thiovinyl]-3-cephem-4-carboxylate (29ca) as a new anti-MRSA parenteral cephalosporin candidate for further biological evaluation. The selected 29ca showed anti-MRSA activity comparable to that of vancomycin (VCM) both in vitro and in vivo, high affinity (IC50=2.7 μg/ml) for penicillin binding protein 2' (PBP2') of MRSA and potent activity against Gram-negative bacteria as well.

Alberto Balsamo - One of the best experts on this subject based on the ideXlab platform.

  • synthesis and inhibitory activity towards human leukocyte elastase of new 7α methoxy and 7α chloro 2 acyloxymethyl cephem derivatives
    European Journal of Medicinal Chemistry, 2001
    Co-Authors: Alberto Balsamo, Daniela Gentili, Simona Rapposelli, Marco Macchia, Giovanni Cercignani, Elisabetta Orlandini, Annalina Lapucci, Armando Rossello
    Abstract:

    Some new cephem derivatives of types 4 and 5, viewed as analogues of type I esters in which the atomic sequence of the C-2 ester group is formally inverted, were synthesised and tested in vitro for their inhibitory activity towards human leukocyte elastase and porcine pancreatic elastase. An examination of the inhibition data obtained for the new type 4 and 5 derivatives, while exhibiting a considerable reduction in their activity against porcine pancreatic elastase, indicated that these compounds still maintain an appreciable inhibitory activity against human leukocyte elastase. On this basis the new type of C-2 substitution appears to contribute to the research of new, potentially interesting, cephalosporinic human leukocyte elastase inhibitors.

  • Synthesis and inhibitory activity towards human leukocyte elastase of new 7 alpha-methoxy and 7 alpha-chloro (2-acyloxymethyl) cephem derivatives
    'Elsevier BV', 2001
    Co-Authors: Alberto Balsamo, Daniela Gentili, Simona Rapposelli, Marco Macchia, Elisabetta Orlandini, Annalina Lapucci, Cercignani G, Armando Rossello
    Abstract:

    Some new cephem derivatives of types 4 and 5, viewed as analogues of type I esters in which the atomic sequence of the C-2 ester group is formally inverted, were synthesised and tested in vitro for their inhibitory activity towards human leukocyte elastase and porcine pancreatic elastase. An examination of the inhibition data obtained for the new type 4 and 5 derivatives, while exhibiting a considerable reduction in their activity against porcine pancreatic elastase, indicated that these compounds still maintain an appreciable inhibitory activity against human leukocyte elastase. On this basis the new type of C-2 substitution appears to contribute to the research of new, potentially interesting, cephalosporinic human leukocyte elastase inhibitors