Literature DB >> 22891714

Malaria-infected mice live until at least day 30 after a new artemisinin-derived thioacetal thiocarbonate combined with mefloquine are administered together in a single, low, oral dose.

Alexander M Jacobine1, Jennifer R Mazzone, Rachel D Slack, Abhai K Tripathi, David J Sullivan, Gary H Posner.   

Abstract

In only three steps and in 21-67% overall yields from the natural trioxane artemisinin, a series of 21 new trioxane C-10 thioacetals was prepared. Upon receiving a single oral dose of only 6 mg/kg of the monomeric trioxane 12c combined with 18 mg/kg of mefloquine hydrochloride, Plasmodium berghei-infected mice survived on average 29.8 days after infection. Two of the four mice in this group had no parasites detectable in their blood on day 30 after infection, and they behaved normally and appeared healthy. One of the mice had 11% blood parasitemia on day 30, and one mouse in this group died on day 29. Of high medicinal importance, the efficacy of this ACT chemotherapy is much better than (almost double) the efficacy under the same conditions using as a positive control the popular trioxane drug artemether plus mefloquine hydrochloride (average survival time of only 16.5 days).

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Year:  2012        PMID: 22891714      PMCID: PMC3460521          DOI: 10.1021/jm3009986

Source DB:  PubMed          Journal:  J Med Chem        ISSN: 0022-2623            Impact factor:   7.446


  43 in total

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Authors:  M Jung; S Lee
Journal:  Bioorg Med Chem Lett       Date:  1998-05-05       Impact factor: 2.823

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Authors:  T S Skinner-Adams; T M Davis; L S Manning; W A Johnston
Journal:  Trans R Soc Trop Med Hyg       Date:  1997 Sep-Oct       Impact factor: 2.184

Review 3.  The therapeutic potential of semi-synthetic artemisinin and synthetic endoperoxide antimalarial agents.

Authors:  Paul M O'Neill
Journal:  Expert Opin Investig Drugs       Date:  2005-09       Impact factor: 6.206

4.  Syntheses and antimalarial activities of 10-substituted deoxoartemisinins.

Authors:  J Ma; E Katz; D E Kyle; H Ziffer
Journal:  J Med Chem       Date:  2000-11-02       Impact factor: 7.446

5.  Orally active antimalarial 3-substituted trioxanes: new synthetic methodology and biological evaluation.

Authors:  G H Posner; J N Cumming; S H Woo; P Ploypradith; S Xie; T A Shapiro
Journal:  J Med Chem       Date:  1998-03-12       Impact factor: 7.446

6.  Growth inhibition activity of thioacetal artemisinin derivatives against human umbilical vein endothelial cells.

Authors:  Sangtae Oh; In Howa Jeong; Woon-Seob Shin; Seokjoon Lee
Journal:  Bioorg Med Chem Lett       Date:  2003-11-03       Impact factor: 2.823

7.  Design, synthesis and biological activity of protaxols.

Authors:  K C Nicolaou; C Riemer; M A Kerr; D Rideout; W Wrasidlo
Journal:  Nature       Date:  1993-07-29       Impact factor: 49.962

Review 8.  Qinghaosu (artemisinin): an antimalarial drug from China.

Authors:  D L Klayman
Journal:  Science       Date:  1985-05-31       Impact factor: 47.728

9.  Synthesis and antiangiogenic activity of thioacetal artemisinin derivatives.

Authors:  Sangtae Oh; In Howa Jeong; Chan Mug Ahn; Woon-Seob Shin; Seokjoon Lee
Journal:  Bioorg Med Chem       Date:  2004-07-15       Impact factor: 3.641

Review 10.  Natural products as starting points for future anti-malarial therapies: going back to our roots?

Authors:  Timothy N C Wells
Journal:  Malar J       Date:  2011-03-15       Impact factor: 2.979

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  5 in total

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3.  Antimalarial chemotherapy: artemisinin-derived dimer carbonates and thiocarbonates.

Authors:  Jennifer R Mazzone; Ryan C Conyers; Abhai K Tripathi; David J Sullivan; Gary H Posner
Journal:  Bioorg Med Chem Lett       Date:  2014-04-16       Impact factor: 2.823

4.  Plasmodium attenuation: connecting the dots between early immune responses and malaria disease severity.

Authors:  Priyanka Fernandes; Roland Frank; Matthew D Lewis; Ann-Kristin Mueller
Journal:  Front Microbiol       Date:  2014-12-02       Impact factor: 5.640

5.  On drug discovery against infectious diseases and academic medicinal chemistry contributions.

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Journal:  Beilstein J Org Chem       Date:  2022-09-29       Impact factor: 2.544

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