Research Topics
| Paul M O'NeillSummaryAffiliation: University of Liverpool Country: UK Publications
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Detail Information
Publications
Rationale design of biotinylated antimalarial endoperoxide carbon centered radical prodrugs for applications in proteomicsVictoria Barton
Department of Chemistry, University of Liverpool, Oxford Street, Liverpool L697ZD, UK
J Med Chem 53:4555-9. 2010..We also describe the synthesis of chemically cleavable linked conjugates designed to enable mild elution of labeled proteins during target protein identification...
Novel, potent, semisynthetic antimalarial carba analogues of the first-generation 1,2,4-trioxane artemetherP M O'Neill
Department of Chemistry, The University of Liverpool, P O Box 147, Liverpool L69 7ZD, U K
J Med Chem 42:5487-93. 1999..On the basis of the products obtained from the in vitro biomimetic Fe(II)-mediated decomposition of 8, the radical mediator of biological activity of this series may be different from that of the parent drug, artemisinin (2)...- Application of thiol-olefin co-oxygenation methodology to a new synthesis of the 1,2,4-trioxane pharmacophorePaul M O'Neill
Department of Chemistry, University of Liverpool, P O Box 147, Liverpool L69 3BX, UK
Org Lett 6:3035-8. 2004..Manipulation of the phenylsulfenyl group in 4a allows for convenient modification to the spiro-trioxane substituents, and we describe, for the first time, the preparation of a new class of antimalarial prodrug... - Design and synthesis of endoperoxide antimalarial prodrug modelsPaul A Stocks
Department of Chemistry, The Robert Robinson Laboratories, University of Liverpool, Liverpool L69 7ZD, UK
Angew Chem Int Ed Engl 43:4193-7. 2004 - Candidate selection and preclinical evaluation of N-tert-butyl isoquine (GSK369796), an affordable and effective 4-aminoquinoline antimalarial for the 21st centuryPaul M O'Neill
Department of Chemistry, University of Liverpool, Liverpool, United Kingdom
J Med Chem 52:1408-15. 2009..This has resulted in the availability of critical information to other drug development teams interested in developing antimalarials within this class... - The molecular mechanism of action of artemisinin--the debate continuesPaul M O'Neill
Department of Chemistry, University of Liverpool, Oxford Street, Liverpool L697ZD, UK
Molecules 15:1705-21. 2010..In this review we will discuss the recent evidence explaining bioactivation and potential molecular targets in the chemotherapy of malaria and cancer... - The therapeutic potential of semi-synthetic artemisinin and synthetic endoperoxide antimalarial agentsPaul M O'Neill
Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, UK
Expert Opin Investig Drugs 14:1117-28. 2005..However, very recent progress with synthetic 1,2,4-trioxolanes provides a new benchmark for future medicinal chemistry efforts in this area... - Enantiomeric 1,2,4-trioxanes display equivalent in vitro antimalarial activity versus Plasmodium falciparum malaria parasites: implications for the molecular mechanism of action of the artemisininsPaul M O'Neill
Department of Chemistry, University of Liverpool, The Robert Robinson Laboratories, Oxford Street, Liverpool, L69 7ZD, UK
Chembiochem 6:2048-54. 2005..In five different P. falciparum isolates, however, the trioxane enantiomers (+)-7 a, (-)-7 a and (+)-7 b, (-)-7 b, showed the same level of in vitro antiparasitic activity... - Diels-Alder/thiol-olefin co-oxygenation approach to antimalarials incorporating the 2,3-dioxabicyclo[3.3.1]nonane pharmacophorePaul M O'Neill
Department of Chemistry, University of Liverpool, PO Box 147, Liverpool L69 3BX, UK
Bioorg Med Chem Lett 16:2991-5. 2006..Reactive C-radical intermediates of this type may be involved in the expression of the antimalarial effect of these bicyclic endoperoxides... - A medicinal chemistry perspective on artemisinin and related endoperoxidesGary H Posner
Department of Chemistry, The Robert Robinson Laboratories, University of Liverpool, Liverpool L69 7ZD, U.K
J Med Chem 47:2945-64. 2004 - Synthesis, antimalarial activity, biomimetic iron(II) chemistry, and in vivo metabolism of novel, potent C-10-phenoxy derivatives of dihydroartemisininP M O'Neill
Robert Robinson Laboratories, University of Liverpool, Liverpool L69 7ZD, England
J Med Chem 44:58-68. 2001.... - A medicinal chemistry perspective on 4-aminoquinoline antimalarial drugsPaul M O'Neill
Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool L67 7ZD UK
Curr Top Med Chem 6:479-507. 2006..Promising new lead compounds undergoing development are described and an overview of physicochemical properties of chloroquine and amodiaquine analogues is also included... - Synthesis, in vitro and in vivo antimalarial assessment of sulfide, sulfone and vinyl amide-substituted 1,2,4-trioxanes prepared via thiol-olefin co-oxygenation (TOCO) of allylic alcoholsRichard Amewu
Department of Chemistry, University of Liverpool, P O Box 147, Liverpool, UK L69 3BX
Org Biomol Chem 8:2068-77. 2010..Selected analogues express potent in vitro nM antimalarial activity, low cytotoxicity and oral activity in the Plasmodium berghei mouse model of malaria... - Synthesis, antimalarial activity, and preclinical pharmacology of a novel series of 4'-fluoro and 4'-chloro analogues of amodiaquine. Identification of a suitable "back-up" compound for N-tert-butyl isoquinePaul M O'Neill
Department of Chemistry, University of Liverpool, Liverpool, UK
J Med Chem 52:1828-44. 2009.... 
Identification, design and biological evaluation of heterocyclic quinolones targeting Plasmodium falciparum type II NADH:quinone oxidoreductase (PfNDH2)Suet C Leung
Department of Chemistry, University of Liverpool, Liverpool, L69 7ZD, UK
J Med Chem 55:1844-57. 2012..falciparum providing the potential added benefit of a dual mechanism of action. The potent oral activity of 2-pyridyl quinolones underlines the potential of this template for further lead optimization studies...- Comparison of the reactivity of antimalarial 1,2,4,5-tetraoxanes with 1,2,4-trioxolanes in the presence of ferrous iron salts, heme, and ferrous iron salts/phosphatidylcholineFatima Bousejra-El Garah
Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, U K
J Med Chem 54:6443-55. 2011..The efficient process of heme alkylation and extensive lipid peroxidation observed here may play a role in the mechanism of action of these two important classes of synthetic endoperoxide antimalarial... - Generation of quinolone antimalarials targeting the Plasmodium falciparum mitochondrial respiratory chain for the treatment and prophylaxis of malariaGiancarlo A Biagini
Molecular and Biochemical Parasitology, Liverpool School of Tropical Medicine, University of Liverpool, Liverpool L3 5QA, United Kingdom
Proc Natl Acad Sci U S A 109:8298-303. 2012.... - Identification, design and biological evaluation of bisaryl quinolones targeting Plasmodium falciparum type II NADH:quinone oxidoreductase (PfNDH2)Chandrakala Pidathala
Department of Chemistry, University of Liverpool, Liverpool, L69 7ZD, UK
J Med Chem 55:1831-43. 2012..Other quinolones presented (e.g., 6d, 6f, 14e) have the capacity to inhibit both PfNDH2 and P. falciparum cytochrome bc(1), and studies to determine the potential advantage of this dual-targeting effect are in progress... - Two-step synthesis of achiral dispiro-1,2,4,5-tetraoxanes with outstanding antimalarial activity, low toxicity, and high-stability profilesGemma L Ellis
Department of Chemistry, University of Liverpool, Liverpool, U K
J Med Chem 51:2170-7. 2008.... - Isoquine and related amodiaquine analogues: a new generation of improved 4-aminoquinoline antimalarialsPaul M O'Neill
Department of Chemistry, The Robert Robinson Laboratories, University of Liverpool, Liverpool L69 7ZD, UK
J Med Chem 46:4933-45. 2003..On the basis of these promising initial studies, isoquine (ISQ1 (3a)) represents a new second generation lead worthy of further investigation as a cost-effective and potentially safer alternative to amodiaquine... - Design and synthesis of orally active dispiro 1,2,4,5-tetraoxanes; synthetic antimalarials with superior activity to artemisininRichard Amewu
Department of Chemistry, University of Liverpool, PO Box 147, Liverpool, UK L69 3BX
Org Biomol Chem 4:4431-6. 2006..Several analogues display an unprecedented level of oral antimalarial activity for this class of endoperoxide drug... - Acridinediones: selective and potent inhibitors of the malaria parasite mitochondrial bc1 complexGiancarlo A Biagini
Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK
Mol Pharmacol 73:1347-55. 2008..falciparum bc(1) Q(o). Dihydroacridinediones represent an entirely new class of bc(1) inhibitors and the potential of these compounds as novel antimalarial drugs is discussed... - Antitumour and antimalarial activity of artemisinin-acridine hybridsMichael Jones
Department of Chemistry, University of Liverpool, Crown Street, Liverpool L69 7ZD, UK
Bioorg Med Chem Lett 19:2033-7. 2009..Strong evidence that the compounds induce apoptosis in HL60 cells was obtained by flow cytometry, which indicated accumulation of cells in the G1 phase of the cell cycle... - Modular synthesis and in vitro and in vivo antimalarial assessment of C-10 pyrrole mannich base derivatives of artemisininBénédicte Pacorel
Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, UK
J Med Chem 53:633-40. 2010.... - Endoperoxide carbonyl falcipain 2/3 inhibitor hybrids: toward combination chemotherapy of malaria through a single chemical entityPeter Gibbons
Department of Chemistry, University of Liverpool, Liverpool, L69 7ZD, UK
J Med Chem 53:8202-6. 2010..Using a proposed target "heme", we also demonstrate heme alkylation/carbonyl inhibitor release and quantitatively measure endoperoxide turnover in parasitized red blood cells... - Examination of the cytotoxic and embryotoxic potential and underlying mechanisms of next-generation synthetic trioxolane and tetraoxane antimalarialsIan M Copple
MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, The University of Liverpool, Sherrington Buildings, Ashton Street, Liverpool, United Kingdom
Mol Med 18:1045-55. 2012.... - Synthesis and biological evaluation of extraordinarily potent C-10 carba artemisinin dimers against P. falciparum malaria parasites and HL-60 cancer cellsJames Chadwick
Department of Chemistry, University of Liverpool, Liverpool, L69 7ZD, UK
Bioorg Med Chem 17:1325-38. 2009.... - Design, synthesis and antimalarial/anticancer evaluation of spermidine linked artemisinin conjugates designed to exploit polyamine transporters in Plasmodium falciparum and HL-60 cancer cell linesJames Chadwick
Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, UK
Bioorg Med Chem 18:2586-97. 2010..Although some limitations in this vector-based approach are apparent, a number of high potency Boc-protected analogues were identified with activity against malaria parasites as low as 0.21nM... - Identification of novel antimalarial chemotypes via chemoinformatic compound selection methods for a high-throughput screening program against the novel malarial target, PfNDH2: increasing hit rate via virtual screening methodsRaman Sharma
Robert Robinson Laboratories, Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, United Kingdom
J Med Chem 55:3144-54. 2012..This study confirms the added value of using multiple ligand-based chemoinformatic approaches and has successfully identified novel distinct chemotypes primed for development as new agents against malaria... - Synthesis and antimalarial activities of a diverse set of triazole-containing furamidine analoguesOlivier Berger
Department of Chemistry, University of Liverpool, Crown Street, Liverpool, L69 3BX UK
ChemMedChem 6:2094-108. 2011..vinckei... - Inhibiting Plasmodium cytochrome bc1: a complex issueVictoria Barton
Department of Chemistry, University of Liverpool, Oxford Street, Liverpool L69 7ZD, UK
Curr Opin Chem Biol 14:440-6. 2010..Significantly, many of these developmental compounds demonstrate little cross resistance with atovaquone-resistant parasite strains, and selected classes have excellent oral activity profiles in rodent models of malaria... - The role of heme and the mitochondrion in the chemical and molecular mechanisms of mammalian cell death induced by the artemisinin antimalarialsAmy E Mercer
Medical Research Council Centre for Drug Safety Science, The University of Liverpool, Liverpool L69 3GE, United Kingdom
J Biol Chem 286:987-96. 2011..36 ± 0.20 μM and 11 ± 5%; and with succinylacetone, >100 μM and 2 ± 5%)... - Convenient syntheses of benzo-fluorinated dibenz[b,f]azepines: rearrangements of isatins, acridines, and indolesEmma Claire Elliott
Robert Robinson Laboratories, Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, UK
Org Lett 13:5592-5. 2011..A range of mono- and difluorinated analogues is accessible, and the syntheses can deliver gram quantities of the final products, which are precursors of fluoro analogues of the important anticonvulsant carbamazepine... - Hepatocellular bioactivation and cytotoxicity of the synthetic endoperoxide antimalarial artefleneJames L Maggs
Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool L69 3GE, UK
Chem Biol Interact 147:173-84. 2004..Cellular glutathione was depleted under these conditions. Therefore arteflene was acutely cytotoxic, though only at relatively high concentrations, when it was metabolized via a pathway which generates carbon-centered radicals... - An efficient route into synthetically challenging bridged achiral 1,2,4,5-tetraoxanes with antimalarial activityGemma L Ellis
Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, UK
Bioorg Med Chem Lett 18:1720-4. 2008..Using this methodology a range of bridged tetraoxanes which display good in vitro antimalarial activity were synthesized... - PfCRT and the trans-vacuolar proton electrochemical gradient: regulating the access of chloroquine to ferriprotoporphyrin IXPatrick G Bray
Department of Molecular and Biochemical Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK
Mol Microbiol 62:238-51. 2006..The efflux of CQ in CQR lines is not directly coupled to the energy supply, consistent with a model in which mutant PfCRT functions as a gated channel or pore, allowing charged CQ species to leak out of the DV... - Metabolic and chemical origins of cross-reactive immunological reactions to arylamine benzenesulfonamides: T-cell responses to hydroxylamine and nitroso derivativesJ Luis Castrejon
MRC Centre for Drug Safety Science, Department of Pharmacology and Therapeutics, The University of Liverpool, Liverpool L69 3GE, United Kingdom
Chem Res Toxicol 23:184-92. 2010..1 h. T-cell cross-reactivity with nitroso sulfonamides provides a mechanistic explanation as to why structurally related arylamine benzenesulfonamides are contraindicated in hypersensitive patients... - Knowledge of the proposed chemical mechanism of action and cytochrome p450 metabolism of antimalarial trioxanes like artemisinin allows rational design of new antimalarial peroxidesGary H Posner
Department of Chemistry, The Johns Hopkins University, Baltimore, MD 21218, USA
Acc Chem Res 37:397-404. 2004..Incorporating metabolism-blocking substituents also provides some new, potent, semi-synthetic artemisinin derivatives... - Orally active, antimalarial, anticancer, artemisinin-derived trioxane dimers with high stability and efficacyGary H Posner
Department of Chemistry, School of Arts and Sciences, The Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218 2685, USA
J Med Chem 46:1060-5. 2003.... - Anticancer and antimalarial efficacy and safety of artemisinin-derived trioxane dimers in rodentsGary H Posner
Department of Chemistry, School of Arts and Sciences, The Johns Hopkins University, 3400 N Charles Street, Baltimore, Maryland 21218 2685, USA
J Med Chem 47:1299-301. 2004..In the transgenic adenocarcinoma of mouse prostate model, some of the trioxane dimers had potent anticancer activity... - Antimalarial and antitumor evaluation of novel C-10 non-acetal dimers of 10beta-(2-hydroxyethyl)deoxoartemisininJ Prince Jeyadevan
Department of Chemistry, The Robert Robinson Laboratories, University of Liverpool, Liverpool L69 7ZD, UK
J Med Chem 47:1290-8. 2004..This observation emphasizes the importance of two trioxane units for high antiproliferative activity, and we propose that the nature of the linker in dimers of this type plays a crucial role in imparting potent anticancer activity... - A short synthesis and biological evaluation of potent and nontoxic antimalarial bridged bicyclic beta-sulfonyl-endoperoxidesMario D Bachi
Department of Organic Chemistry, The Weizmann Institute of Science, Rehovot 76100, Israel
J Med Chem 46:2516-33. 2003..NS. In view of the nontoxicity of beta-sulfonyl peroxides 39a, 46a, and 46b in mice, at high dosing, these compounds are regarded as promising antimalarial drug candidates... - Mild, fast, and stereoselective epoxide opening by ketone enolate anions. Application to synthesis of the norlignan curculigineGary H Posner
Department of Chemistry, School of Arts and Sciences, The Johns Hopkins University, Baltimore, MD 21218, USA
J Org Chem 68:3049-54. 2003.... - Malaria-infected mice are cured by oral administration of new artemisinin derivativesGary H Posner
Department of Chemistry, School of Arts and Sciences, The Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218 2685, USA
J Med Chem 51:1035-42. 2008..7-13.7, and this effect is comparable to that of the fully synthetic trioxolane drug development candidate OZ277, which is in phase II clinical trials... - Electronically stabilized versions of the antimalarial acetal trioxanes artemether and artesunateGary H Posner
Department of Chemistry, The Johns Hopkins University, 3400 N Charles Street, Baltimore, MD 21218, USA
Bioorg Med Chem 16:5247-53. 2008..The very strong inductive electron-withdrawing C-9 substituent is shown to retard considerably C-10 ionization (acid-promoted etherification) of 9-fluoro-DHA and 9-sulfonyl-DHA... - In vitro inhibition of Toxoplasma gondii by four new derivatives of artemisininLorraine Jones-Brando
Stanley Division of Developmental Neurovirology, Dept of Pediatrics, Johns Hopkins University School of Medicine, 600 N Wolfe St, Baltimore, MD 21287 4988, USA
Antimicrob Agents Chemother 50:4206-8. 2006..We synthesized novel, nonacetal, hydrolytically stable derivatives of artemisinin and showed that they inhibit the replication of Toxoplasma gondii in cell culture... - Antimalarial chemotherapeutic peroxides: artemisinin, yingzhaosu A and related compoundsKristina Borstnik
Department of Chemistry, The Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218-2685, USA
Int J Parasitol 32:1661-7. 2002..This review summarises recent achievements in this area of peroxide drug development for malaria chemotherapy... - Second generation, orally active, antimalarial, artemisinin-derived trioxane dimers with high stability, efficacy, and anticancer activityIk-Hyeon Paik
Department of Chemistry, The Johns Hopkins University, Baltimore, Maryland 21218-2685, USA
J Med Chem 49:2731-4. 2006.... - Malaria: new chemotherapeutic peroxide drugsKristina Borstnik
Department of Chemistry, The Johns Hopkins University, Baltimore, MD 21218, USA
Mini Rev Med Chem 2:573-83. 2002..This review summarizes recent achievements in this area of peroxide drug development for malaria chemotherapy... - Orally active, water-soluble antimalarial 3-aryltrioxanes: short synthesis and preclinical efficacy testing in rodentsGary H Posner
Department of Chemistry, School of Arts and Sciences, The Johns Hopkins University, 3400 N Charles Street, Baltimore, Maryland 21218 2685, USA
J Med Chem 45:3824-8. 2002..4 than is artelinic acid (1), a leading semisynthetic, herb-derived antimalarial trioxane drug candidate... - New chemical and biological aspects of artemisinin-derived trioxane dimersGary H Posner
Department of Chemistry, School of Arts and Sciences, The Johns Hopkins University, Baltimore, MD 21218, USA
Bioorg Med Chem 10:227-32. 2002..Each dimer was evaluated in vitro for antimalarial, antiproliferative, and antitumor activities; ketone dimers and, more than fluorinated dimers and, are promising for chemotherapy of both malaria and cancer... - Malaria-infected mice are cured by a single dose of novel artemisinin derivativesGary H Posner
Department of Chemistry, School of Arts and Sciences, The Johns Hopkins Malaria Research Institute, Johns Hopkins University, Baltimore, Maryland 21218, USA
J Med Chem 50:2516-9. 2007..Four of these trioxane dimers cure malaria-infected mice after only a single subcutaneous dose, and two other dimers cure after three oral doses... - Vitamin D analogs as modulators of vitamin D receptor actionSara Peleg
Department of Endocrine Neoplasia and Hormonal Disorders, Box 435, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
Curr Top Med Chem 3:1555-72. 2003..Finally, we will describe the current and potential use of these selective modulators of the VDR for treatment of human diseases such as osteoporosis, cancer, and secondary hyperparathyroidism... - Conceptually new low-calcemic oxime analogues of the hormone 1 alpha,25-dihydroxyvitamin D(3): synthesis and biological testingGary H Posner
Department of Chemistry, School of Arts and Sciences, The Johns Hopkins University, Baltimore, Maryland 21218, USA
J Med Chem 45:1723-30. 2002..In terms of in vivo toxicity (hypercalcemia), ketone 2b is strongly calcemic in rats, whereas oxime 3b and oxime ether 4b are considerably less calcemic (i.e., safer) than calcitriol (1)... - Less calcemic Vitamin D analogs enhance creatine kinase specific activity and modulate responsiveness to gonadal steroids in the vasculatureDalia Somjen
Institute of Endocrinology, Metabolism and Hypertension, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel
J Steroid Biochem Mol Biol 101:232-8. 2006..These results corroborate our previous in vitro studies in human vascular cells and further suggest that the Vitamin D system plays an important physiological role in maintaining normal cell energy reservoir in the vasculature... - Low-calcemic vitamin D analogs (deltanoids) for human cancer preventionGary H Posner
Department of Chemistry, The Johns Hopkins University, Baltimore, MD 21218, USA
J Nutr 132:3802S-3803S. 2002..A short summary is provided of leading chemopreventive analogs of vitamin D3... - Difluoromethyl analogs of the natural hormone 1alpha,25-dihydroxyvitamin D3: Design, synthesis, and preliminary biological evaluationGary H Posner
Department of Chemistry, The Johns Hopkins University, Baltimore, MD 21218, USA
J Steroid Biochem Mol Biol 103:213-21. 2007..The transcriptional activity of the 25-CHF(2) analog 3 is higher than that of the 1-CHF(2) analog 4... - Unexpected steric effects of "remote" alkyl groups on the rate of conjugate additions to alkyl alpha,beta-ethylenic sulfones, sulfoxides, and estersAimee R Usera
Department of Chemistry, School of Arts and Sciences, The Johns Hopkins University, Baltimore, Maryland 21218, USA
J Org Chem 72:2329-34. 2007..Competition experiments establish the relative rates of Michael additions to be in the following order: Et>i-Pr>t-Bu... - Antiproliferative, low-calcemic, fluorinated sulfone analogs of 1alpha,25-dihydroxyvitamin D3: chemical synthesis and biological evaluationAimee R Usera
Department of Chemistry, School of Arts and Sciences, The Johns Hopkins University, Baltimore, MD 21218, USA
Bioorg Med Chem 15:5509-18. 2007..Incorporation of additional fluorines, as in a perfluorobutyl analog, results in a loss of antiproliferative activity... - Low-calcemic, highly antiproliferative, 23-oxa ether analogs of the natural hormone 1 alpha,25-dihydroxyvitamin D3: design, synthesis, and preliminary biological evaluationKimberly S Petersen
Department of Chemistry, School of Arts and Sciences, The Johns Hopkins University, Baltimore, MD 21218, USA
J Med Chem 50:5824-32. 2007..One of these three 23-oxa analogs has transcriptional potency almost as high as that of calcitriol, even though it binds to the human vitamin D receptor only about 1% as well as calcitriol... - Low-calcemic, highly antiproliferative, 1-difluoromethyl hybrid analogs of the natural hormone 1alpha,25-dihydroxyvitamin D3: design, synthesis, and preliminary biological evaluationSara Peleg
Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas, M.D. Anderson Cancer Center, Houston, Texas 77030, USA
J Med Chem 49:7513-7. 2006..Both of these two hybrid analogs are as transcriptionally active as calcitriol and are strongly antiproliferative in vitro but are low-calcemic in vivo... - Biological mechanisms of action of novel C-10 non-acetal trioxane dimers in prostate cancer cell linesAdebusola A Alagbala
Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA
J Med Chem 49:7836-42. 2006..TDs also promoted apoptosis in LNCaP cells with increased expression of proapoptotic bax. These results demonstrate that TDs are potentially useful agents that warrant further preclinical development for treatment of prostate cancer... - Inhibition of prostate cancer-meditated osteoblastic bone lesions by the low-calcemic analog 1alpha-hydroxymethyl-16-ene-26,27-bishomo-25-hydroxy vitamin D3Sara Peleg
Department of Endocrine Neoplasia and Hormonal Disorders, Unit 435, The University of Texas, M D Anderson Cancer Center, Houston, TX 77030, USA
J Steroid Biochem Mol Biol 97:203-11. 2005..These experiments led to the hypothesis that, in vivo, JK-1626-2 prevented the metastatic bone lesions by inhibiting the mitogenic response of osteoblasts to growth factors produced by MDA-PCa 2b cells... - Highly antiproliferative, low-calcemic, side-chain ketone analogs of the hormone 1alpha,25-dihydroxyvitamin D3Gary H Posner
Department of Chemistry, The Johns Hopkins University, Baltimore, MD 21218, USA
Bioorg Med Chem 13:5569-80. 2005..In addition, ketone analog 19-nor-2a is not significantly less calcemic in vivo than 19-methylene analog 2a... - Effect of artemisinins and other endoperoxides on nitric oxide-related signaling pathway in RAW 264.7 mouse macrophage cellsV Badireenath Konkimalla
German Cancer Research Center, Pharmaceutical Biology C015, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
Nitric Oxide 19:184-91. 2008..In addition, other signaling pathways also contribute to the inhibitory effect of artesunate towards RAW 264.7 cells pointing to a multi-factorial mode of action of artesunate... - A-ring hydroxymethyl 19-nor analogs of the natural hormone 1alpha,25-dihydroxyvitamin D(3): synthesis and preliminary biological evaluationMark A Hatcher
Department of Chemistry, The Johns Hopkins University, Baltimore, MD 21218, USA
Bioorg Med Chem 13:3964-76. 2005.... - Novel A-ring analogs of the hormone 1alpha,25-dihydroxyvitamin D3: synthesis and preliminary biological evaluationGary H Posner
Department of Chemistry, The Johns Hopkins University, Baltimore, MD 21218, USA
Bioorg Med Chem 13:2959-66. 2005.... - Highly antiproliferative, low-calcemic, side-chain amide and hydroxamate analogs of the hormone 1alpha,25-dihydroxyvitamin D3Sandra Sinishtaj
Department of Chemistry, The Johns Hopkins University, Baltimore, MD 21218, USA
Bioorg Med Chem 14:6341-8. 2006..Even though lacking the 25-OH group characteristic of natural calcitriol (1), analogs 2-4 are as antiproliferative in vitro as calcitriol (1) but are 20-40 times less calciuric in vivo than calcitriol (1)... - Low-calcemic, efficacious, 1alpha,25-dihydroxyvitamin D3 analog QW-1624F2-2: calcemic dose-response determination, preclinical genotoxicity testing, and revision of A-ring stereochemistryGary H Posner
Department of Chemistry, The Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA
Steroids 69:757-62. 2004..This analog is shown to be approximately 80-100 times less calciuric than the natural hormone 1alpha,25-dihydoxyvitamin D3. This analog is shown also to be non-genotoxic in three different standard assays... - Potent, selective and low-calcemic inhibitors of CYP24 hydroxylase: 24-sulfoximine analogues of the hormone 1alpha,25-dihydroxyvitamin D(3)Mehmet Kahraman
Department of Chemistry, School of Arts and Sciences, The Johns Hopkins University, Baltimore, MD 21218, USA
J Med Chem 47:6854-63. 2004..4 nM) having low calcemic activity. In addition, this compound shows high selectivity toward the CYP24 enzyme in comparison to CYP27A1 (IC(50) > 1000 nM) and CYP27B (IC(50) = 554 nM)...