J L Vennerstrom

Summary

Affiliation: University of Nebraska Medical Center
Country: USA

Publications

  1. ncbi request reprint Synthesis and antimalarial activity of sixteen dispiro-1,2,4, 5-tetraoxanes: alkyl-substituted 7,8,15,16-tetraoxadispiro[5.2.5. 2]hexadecanes
    J L Vennerstrom
    College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, Nebraska 68198 6025, USA
    J Med Chem 43:2753-8. 2000
  2. ncbi request reprint Identification of an antimalarial synthetic trioxolane drug development candidate
    Jonathan L Vennerstrom
    College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, Nebraska 68198 6025, USA
    Nature 430:900-4. 2004
  3. ncbi request reprint Synthesis and antimalarial activity of 11 dispiro-1,2,4,5-tetraoxane analogues of WR 148999. 7,8,15,16-Tetraoxadispiro[5.2.5.2]hexadecanes substituted at the 1 and 10 positions with unsaturated and polar functional groups
    Y Dong
    College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, Nebraska 68198 6025, USA
    J Med Chem 42:1477-80. 1999
  4. ncbi request reprint Assessment of the antimalarial potential of tetraoxane WR 148999
    J L Vennerstrom
    College of Pharmacy, University of Nebraska Medical Center, Omaha 68198 6025, USA
    Am J Trop Med Hyg 62:573-8. 2000
  5. pmc 8-Aminoquinolines active against blood stage Plasmodium falciparum in vitro inhibit hematin polymerization
    J L Vennerstrom
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha 68198 6025
    Antimicrob Agents Chemother 43:598-602. 1999
  6. ncbi request reprint Spiro- and dispiro-1,2-dioxolanes: contribution of iron(II)-mediated one-electron vs two-electron reduction to the activity of antimalarial peroxides
    Xiaofang Wang
    College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, Nebraska, USA
    J Med Chem 50:5840-7. 2007
  7. ncbi request reprint Mechanisms of in situ activation for peroxidic antimalarials
    Yuxiang Dong
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska 68198 6025, USA
    Redox Rep 8:284-8. 2003
  8. ncbi request reprint Dispiro-1,2,4-trioxane analogues of a prototype dispiro-1,2,4-trioxolane: mechanistic comparators for artemisinin in the context of reaction pathways with iron(II)
    Yuanqing Tang
    College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE 68198 6025, USA
    J Org Chem 70:5103-10. 2005
  9. ncbi request reprint Spiro and dispiro-1,2,4-trioxolanes as antimalarial peroxides: charting a workable structure-activity relationship using simple prototypes
    Yuxiang Dong
    College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, Nebraska 68198 6025, USA
    J Med Chem 48:4953-61. 2005
  10. ncbi request reprint Systemic and ocular pharmacokinetics of N-4-benzoylaminophenylsulfonylglycine (BAPSG), a novel aldose reductase inhibitor
    Gangadhar Sunkara
    Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198 6025, USA
    J Pharm Pharmacol 56:351-8. 2004

Collaborators

Detail Information

Publications35

  1. ncbi request reprint Synthesis and antimalarial activity of sixteen dispiro-1,2,4, 5-tetraoxanes: alkyl-substituted 7,8,15,16-tetraoxadispiro[5.2.5. 2]hexadecanes
    J L Vennerstrom
    College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, Nebraska 68198 6025, USA
    J Med Chem 43:2753-8. 2000
    ..There was no apparent relationship between tetraoxane structure and in vitro neurotoxicity, nor was there any correlation between antimalarial activity and neurotoxicity for these seventeen tetraoxanes...
  2. ncbi request reprint Identification of an antimalarial synthetic trioxolane drug development candidate
    Jonathan L Vennerstrom
    College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, Nebraska 68198 6025, USA
    Nature 430:900-4. 2004
    ..Here we describe how a synthetic peroxide antimalarial drug development candidate was identified in a collaborative drug discovery project...
  3. ncbi request reprint Synthesis and antimalarial activity of 11 dispiro-1,2,4,5-tetraoxane analogues of WR 148999. 7,8,15,16-Tetraoxadispiro[5.2.5.2]hexadecanes substituted at the 1 and 10 positions with unsaturated and polar functional groups
    Y Dong
    College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, Nebraska 68198 6025, USA
    J Med Chem 42:1477-80. 1999
    ....
  4. ncbi request reprint Assessment of the antimalarial potential of tetraoxane WR 148999
    J L Vennerstrom
    College of Pharmacy, University of Nebraska Medical Center, Omaha 68198 6025, USA
    Am J Trop Med Hyg 62:573-8. 2000
    ....
  5. pmc 8-Aminoquinolines active against blood stage Plasmodium falciparum in vitro inhibit hematin polymerization
    J L Vennerstrom
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha 68198 6025
    Antimicrob Agents Chemother 43:598-602. 1999
    ....
  6. ncbi request reprint Spiro- and dispiro-1,2-dioxolanes: contribution of iron(II)-mediated one-electron vs two-electron reduction to the activity of antimalarial peroxides
    Xiaofang Wang
    College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, Nebraska, USA
    J Med Chem 50:5840-7. 2007
    ....
  7. ncbi request reprint Mechanisms of in situ activation for peroxidic antimalarials
    Yuxiang Dong
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska 68198 6025, USA
    Redox Rep 8:284-8. 2003
    ..It also presents a useful link between the mode of action of artemisinin and that of chloroquine, and highlights redox cycles involved in the interaction between the drug and vital biomolecules...
  8. ncbi request reprint Dispiro-1,2,4-trioxane analogues of a prototype dispiro-1,2,4-trioxolane: mechanistic comparators for artemisinin in the context of reaction pathways with iron(II)
    Yuanqing Tang
    College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE 68198 6025, USA
    J Org Chem 70:5103-10. 2005
    ..These data suggest that formation of either primary or secondary carbon-centered radicals is a necessary but insufficient criterion for antimalarial activity of 1 and synthetic peroxides...
  9. ncbi request reprint Spiro and dispiro-1,2,4-trioxolanes as antimalarial peroxides: charting a workable structure-activity relationship using simple prototypes
    Yuxiang Dong
    College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, Nebraska 68198 6025, USA
    J Med Chem 48:4953-61. 2005
    ..In pharmacokinetic experiments, four trioxolanes had high plasma clearance values, suggesting a potential metabolic instability. The toxicological profiles of two trioxolanes were comparable to that of artesunate...
  10. ncbi request reprint Systemic and ocular pharmacokinetics of N-4-benzoylaminophenylsulfonylglycine (BAPSG), a novel aldose reductase inhibitor
    Gangadhar Sunkara
    Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198 6025, USA
    J Pharm Pharmacol 56:351-8. 2004
    ..Thus, BAPSG was distributed to ocular tissues following systemic and topical modes of administration...
  11. ncbi request reprint Immunization to nicotine with a peptide-based vaccine composed of a conformationally biased agonist of C5a as a molecular adjuvant
    Sam D Sanderson
    School of Allied Health Professions, University of Nebraska Medical Center, 985155 Nebraska Medical Center, Omaha, NE 68198 5155, USA
    Int Immunopharmacol 3:137-46. 2003
    ....
  12. pmc Comparative antimalarial activities of six pairs of 1,2,4,5-tetraoxanes (peroxide dimers) and 1,2,4,5,7,8-hexaoxonanes (peroxide trimers)
    Yuxiang Dong
    College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE 68198 6025, USA
    Antimicrob Agents Chemother 51:3033-5. 2007
    ..The lack of iron-mediated reactivity of the hexaoxonanes may explain their low activity compared to the tetraoxanes, the latter of which are able to undergo iron(II)-mediated activation...
  13. doi request reprint The structure-activity relationship of the antimalarial ozonide arterolane (OZ277)
    Yuxiang Dong
    College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE, USA
    J Med Chem 53:481-91. 2010
    ..berghei-infected mice. Five new ozonides with antimalarial efficacy and ADME profiles superior or equal to that of arterolane were identified...
  14. doi request reprint Characterization of the two major CYP450 metabolites of ozonide (1,2,4-trioxolane) OZ277
    Lin Zhou
    College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE 68198, USA
    Bioorg Med Chem Lett 18:1555-8. 2008
    ..The antimalarial synthetic ozonide OZ277 (RBx11160) was hydroxylated by human liver microsomes at the distal bridgehead carbon atoms of the spiroadamantane substructure to form two carbinol metabolites devoid of antimalarial activity...
  15. ncbi request reprint Antimalarial activity of N-alkyl amine, carboxamide, sulfonamide, and urea derivatives of a dispiro-1,2,4-trioxolane piperidine
    Maniyan Padmanilayam
    College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE, USA
    Bioorg Med Chem Lett 16:5542-5. 2006
    ..20 to 7.0 ng/mL. The oral efficacies of two of these were superior to artesunate and comparable to artemether. The attractive chemical simplicity of these compounds is balanced only by an apparent metabolic susceptibility...
  16. ncbi request reprint Synthesis and solution properties of deferoxamine amides
    P M Ihnat
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, Nebraska 68198 6025, USA
    J Pharm Sci 89:1525-36. 2000
    ....
  17. pmc Phenolic bis-styrylbenzenes as β-amyloid binding ligands and free radical scavengers
    Daniel P Flaherty
    University of Nebraska Medical Center, College of Pharmacy, 986025 Nebraska Medical Center, Omaha, Nebraska 68198, USA
    J Med Chem 53:7992-9. 2010
    ..By use of a DPPH assay, phenol functional groups with para orientations seem to be a necessary, but insufficient, criterion for good free radical scavenging properties in these compounds...
  18. ncbi request reprint Effect of functional group polarity on the antimalarial activity of spiro and dispiro-1,2,4-trioxolanes
    Yuxiang Dong
    College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE, USA
    Bioorg Med Chem 14:6368-82. 2006
    ..More lipophilic trioxolanes tended to have better oral activities than their more polar counterparts. Trioxolanes with a wide range of neutral and basic, but not acidic, functional groups had good antimalarial profiles...
  19. doi request reprint The comparative antimalarial properties of weak base and neutral synthetic ozonides
    Yuanqing Tang
    College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE, USA
    Bioorg Med Chem Lett 20:563-6. 2010
    ..A wide range of LogP/D(pH)(7.4) values were tolerated, although more lipophilic ozonides tended to be less metabolically stable...
  20. doi request reprint Spiroadamantyl 1,2,4-trioxolane, 1,2,4-trioxane, and 1,2,4-trioxepane pairs: relationship between peroxide bond iron(II) reactivity, heme alkylation efficiency, and antimalarial activity
    Xiaofang Wang
    College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE, USA
    Bioorg Med Chem Lett 19:4542-5. 2009
    ....
  21. ncbi request reprint Carbon isosteres of the 4-aminopyridine substructure of chloroquine: effects on pK(a), hematin binding, inhibition of hemozoin formation, and parasite growth
    Srinivasa R Cheruku
    College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, Nebraska 68198 6025, USA
    J Med Chem 46:3166-9. 2003
    ..falciparum in vitro. Evidently, the CQ-hematin interaction is largely a function of its pyridine substructure, but inhibition of hemozoin formation and parasite growth depends on its 4-aminopyridine substructure...
  22. ncbi request reprint Synthetic peroxides as antimalarials
    Yuanqing Tang
    College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska, USA
    Med Res Rev 24:425-48. 2004
    ..Nonetheless, substantial progress has been made in the identification of a new generation of synthetic antimalarial peroxides...
  23. pmc Structure-activity relationship of an ozonide carboxylic acid (OZ78) against Fasciola hepatica
    Qingjie Zhao
    College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska, USA
    J Med Chem 53:4223-33. 2010
    ..This study also showed that the activity of 1 is peroxide-bond-dependent, suggesting that its flukicidal efficacy depends upon hemoglobin digestion in F. hepatica...
  24. ncbi request reprint Polyfluorinated bis-styrylbenzene beta-amyloid plaque binding ligands
    Daniel P Flaherty
    University of Nebraska Medical Center, College of Pharmacy, 986025 Nebraska Medical Center, Omaha, Nebraska 68198, USA
    J Med Chem 50:4986-92. 2007
    ..These data extend the SAR of bis-styrylbenzene Abeta binding and provide direction for the development of a noninvasive probe for early detection of Alzheimer's disease using 19F MRI...
  25. ncbi request reprint Weak base dispiro-1,2,4-trioxolanes: potent antimalarial ozonides
    Yuanqing Tang
    College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE, USA
    Bioorg Med Chem Lett 17:1260-5. 2007
    ..Guanidine, aminoxy, and amino acid trioxolanes had poor antimalarial activity. Lipophilic trioxolanes were less stable metabolically than their more polar counterparts...
  26. pmc Peroxide bond-dependent antiplasmodial specificity of artemisinin and OZ277 (RBx11160)
    Marcel Kaiser
    Swiss Tropical Institute, Basel, Switzerland
    Antimicrob Agents Chemother 51:2991-3. 2007
    ..In contrast, the weak activities of artemisinin and OZ277 against six other protozoan parasites were peroxide bond independent. These data support the iron-dependent artemisinin alkylation hypothesis...
  27. pmc Relationship between antimalarial activity and heme alkylation for spiro- and dispiro-1,2,4-trioxolane antimalarials
    Darren J Creek
    Centre for Drug Candidate Optimisation, Victorian College of Pharmacy, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia
    Antimicrob Agents Chemother 52:1291-6. 2008
    ..Significantly less heme alkylation was observed for the clinically utilized artemisinin derivatives compared to the equipotent trioxolanes included in this study...
  28. ncbi request reprint Oxidative stress in malaria parasite-infected erythrocytes: host-parasite interactions
    Katja Becker
    Interdisciplinary Research Center, Heinrich Buff Ring 26 32, Justus Liebig University, D 35392 Giessen, Germany
    Int J Parasitol 34:163-89. 2004
    ..Indeed, a number of currently used drugs, especially the endoperoxide antimalarials, appear to act by increasing oxidant stress, and novel drugs such as peroxidic compounds and anthroquinones are being developed...
  29. ncbi request reprint Activity of artemether and OZ78 against triclabendazole-resistant Fasciola hepatica
    Jennifer Keiser
    Department of Medical Parasitology and Infection Biology, Swiss Tropical Institute, P O Box, CH 4002 Basel, Switzerland
    Trans R Soc Trop Med Hyg 101:1219-22. 2007
    ..hepatica isolate, and hence these drugs might become useful in areas where triclabendazole resistance is common...
  30. ncbi request reprint Iron-mediated degradation kinetics of substituted dispiro-1,2,4-trioxolane antimalarials
    Darren J Creek
    Centre for Drug Candidate Optimisation, Victorian College of Pharmacy, Monash University Parkville Campus, 381 Royal Parade, Parkville, Victoria 3052, Australia
    J Pharm Sci 96:2945-56. 2007
    ..A wide range of reaction rates was observed within this class of peroxide antimalarials, however iron-mediated reactivity did not directly correlate with in vitro antimalarial activity...
  31. ncbi request reprint A refined pharmacophore identifies potent 4-amino-7-chloroquinoline-based inhibitors of the botulinum neurotoxin serotype A metalloprotease
    James C Burnett
    SAIC Frederick, Inc, Target Structure Based Drug Discovery Group, Frederick, Frederick, Inc, National Cancer Institute at Frederick, P O Box B, F V C 310, Frederick, Maryland 21702, USA
    J Med Chem 50:2127-36. 2007
    ..Finally, structural motifs of the new SMNPIs, as well as two structure-based derivatives, were examined for activity, providing valuable information about pharmacophore component contributions to inhibition...
  32. pmc In vitro and in vivo activities of synthetic trioxolanes against major human schistosome species
    Shu Hua Xiao
    National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Shanghai, People s Republic of China
    Antimicrob Agents Chemother 51:1440-5. 2007
    ..2 to 100%. Our results, along with the low toxicity, metabolic stability, and good pharmacokinetic properties of the OZs, indicate the potential for the development of novel broad-spectrum antischistosomal OZ drug candidates...
  33. ncbi request reprint The synthetic peroxide OZ78 is effective against Echinostoma caproni and Fasciola hepatica
    Jennifer Keiser
    Swiss Tropical Institute, CH 4002 Basel, Switzerland
    J Antimicrob Chemother 58:1193-7. 2006
    ..The trematocidal properties of a synthetic peroxide, 1,2,4-trioxolane (OZ78) were determined both in vivo and in vitro...
  34. ncbi request reprint Conformational sampling of the botulinum neurotoxin serotype A light chain: implications for inhibitor binding
    James C Burnett
    Developmental Therapeutics Program, NCI Frederick, Frederick, MD 21702, USA
    Bioorg Med Chem 13:333-41. 2005
    ..The results from these studies may aid in the future identification/development of more potent small molecule inhibitors that take advantage of new binding contacts in the BoNT/A LC...
  35. ncbi request reprint Chemical kinetics and aqueous degradation pathways of a new class of synthetic ozonide antimalarials
    Christine S Perry
    Centre for Drug Candidate Optimisation, Victorian College of Pharmacy, Monash University, Parkville Campus, Victoria 3052, Australia
    J Pharm Sci 95:737-47. 2006
    ....