Martin A Shapiro

Publications (4)10.36 Total impact

• Article: Structure-activity relationships of 3-aminoquinazolinediones, a new class of bacterial type-2 topoisomerase (DNA gyrase and topo IV) inhibitors.

  Tuan P Tran, Edmund L Ellsworth, Joseph P Sanchez, Brian M Watson, Michael A Stier, H D Hollis Showalter, John M Domagala, Martin A Shapiro, E Themis Joannides, Stephen J Gracheck, Dai Q Nguyen, Paul Bird, Judy Yip, Anurag Sharadendu, Chan Ha, Saeed Ramezani, Xiujuan Wu, Rajeshwar Singh
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  ABSTRACT: A series of 3-aminoquinazolinediones was synthesized and evaluated for its antibacterial and DNA gyrase activity. The SAR around the quinazolinedione core was explored and the optimal substitutions were combined to give two compounds, 2r and 2s, with exceptional enzyme potency (IC50 = 0.2 microM) and activity against gram-positive organisms (MIC's = 0.015-0.06 microg/mL).
  Bioorganic & Medicinal Chemistry Letters 04/2007; 17(5):1312-20. · 2.55 Impact Factor
• Article: 3-aminoquinazolinediones as a new class of antibacterial agents demonstrating excellent antibacterial activity against wild-type and multidrug resistant organisms.

  Edmund L Ellsworth, Tuan P Tran, H D Hollis Showalter, Joseph P Sanchez, Brian M Watson, Michael A Stier, John M Domagala, Stephen J Gracheck, E Themis Joannides, Martin A Shapiro, Steve A Dunham, Debra L Hanna, Michael D Huband, Jeffrey W Gage, Joel C Bronstein, Jia Yeu Liu, Dai Q Nguyen, Rajeshwar Singh
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  ABSTRACT: The 3-aminoquinzolinediones represent a new series of antibacterial agents structurally related to the fluoroquinolones. They are inhibitors of bacterial gyrase and topoisomerase IV and demonstrate clinically useful antibacterial activity against fastidious Gram-negative and Gram-positive organisms, including multidrug- and fluoroquinolone-resistant organisms. These agents also demonstrate in vivo efficacy in murine systemic infection models.
  Journal of Medicinal Chemistry 12/2006; 49(22):6435-8. · 5.25 Impact Factor
• Article: Synthesis and structural-activity relationships of 3-hydroxyquinazoline-2,4-dione antibacterial agents.

  Tuan P Tran, Edmund L Ellsworth, Michael A Stier, John M Domagala, H D Hollis Showalter, Stephen J Gracheck, Martin A Shapiro, Themis E Joannides, Rajeshwar Singh
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  ABSTRACT: A series of 3-hydroxyquinazoline-2,4-diones was synthesized and evaluated for antibacterial activity. This series represents a novel addition to the DNA gyrase inhibitor class of antibacterials. Appropriate substitutions onto the core template yielded compounds with excellent potency against E. coli gyrase and significant in vitro Gram-negative and Gram-positive antibacterial activity.
  Bioorganic & Medicinal Chemistry Letters 10/2004; 14(17):4405-9. · 2.55 Impact Factor
• Article: Comparative chemotherapeutic acitivity of new fluorinated 4-quinolones and standard agents against a variety of bacteria in a mouse infection model

  Josephine C. Sesnie, Peter W. Fritsch, Timothy J. Griffin, Carl L. Heifetz, Evangeline T. Leopold, Thomas E. Malta, Martin A. Shapiro, Patrick Vincent
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  ABSTRACT: The new fluorinated 4-quinolones appear to represent orally effective alternatives to parenteral and oral agents currently in use. A number of new fluorinated 4-quinolones were compared in acute systemic mouse-infection models with various Gram-positive cocci (streptococci and staphylococci), Enterobacteriaceae and Pseudomonas aeruginosa . Also included were standard oral and parenteral antimicrobial agents. CI-934 was the most potent quinolone in infections induced by Streptococcus pyogenes and Str. pneumoniae . CI-934, ciprofloxacin, enoxacin, norfloxacin, ofloxacin and pefloxacin were as effective as or superior to standard oral agents currently utilized in infections induced by the Enterobacteriaceae and staphylococci. They were active against antibiotic-susceptible strains and strains resistant to β -lactams and gentamicin. Most were also quite potent against systemic P. aeruginosa mouse infections. These studies indicate good chemotherapeutic potential for the new generation fluorinated 4-quinolones in infections induced by the staphylococci, streptococci, Enterobacteriaceae and P. aeruginosa , including strains resistant to standard antimicrobial agents.