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Literature DB >> 24936235

1,4-naphthoquinone cations as antiplasmodial agents: hydroxy-, acyloxy-, and alkoxy-substituted analogues.

Xiao Lu¹, Ali Altharawi¹, Jiri Gut², Philip J Rosenthal², Timothy E Long³.

Abstract

Cations of hydroxy-substituted 1,4-naphthoquinones were synthesized and evaluated as antiplasmodial agents against Plasmodium falciparum. The atovaquone analogues were found to be inactive as antagonists of parasite growth, which was attributed to ionization of the acidic hydroxyl moiety. Upon modification to an alkoxy substituent, the antiplasmodial activity was restored in the sub-100 nM range. Optimal inhibitors were found to possess IC50 values of 17.4-49.5 nM against heteroresistant P. falciparum W2.

Entities: Chemical Species

Keywords: 1,4-naphthoquinones; Plasmodium; malaria; phosphonium cations

Year: 2012 PMID： 24936235 PMCID： PMC4056940 DOI： 10.1021/ml300242v

Source DB: PubMed Journal: ACS Med Chem Lett ISSN： 1948-5875 Impact factor: 4.345

17 in total

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Authors: Giancarlo A Biagini; Nicholas Fisher; Alison E Shone; Murad A Mubaraki; Abhishek Srivastava; Alisdair Hill; Thomas Antoine; Ashley J Warman; Jill Davies; Chandrakala Pidathala; Richard K Amewu; Suet C Leung; Raman Sharma; Peter Gibbons; David W Hong; Bénédicte Pacorel; Alexandre S Lawrenson; Sitthivut Charoensutthivarakul; Lee Taylor; Olivier Berger; Alison Mbekeani; Paul A Stocks; Gemma L Nixon; James Chadwick; Janet Hemingway; Michael J Delves; Robert E Sinden; Anne-Marie Zeeman; Clemens H M Kocken; Neil G Berry; Paul M O'Neill; Stephen A Ward
Journal: Proc Natl Acad Sci U S A Date: 2012-05-07 Impact factor: 11.205

Review 9. Mitochondrial pharmacology.

Authors: Robin A J Smith; Richard C Hartley; Helena M Cochemé; Michael P Murphy
Journal: Trends Pharmacol Sci Date: 2012-04-18 Impact factor: 14.819

1,4-naphthoquinone cations as antiplasmodial agents: hydroxy-, acyloxy-, and alkoxy-substituted analogues.

Review 1. Antiparasitic agent atovaquone.

2. Drug discovery: Priming the antimalarial pipeline.

3. Experimental evidence for proton motive force-dependent catalysis by the diheme-containing succinate:menaquinone oxidoreductase from the Gram-positive bacterium Bacillus licheniformis.

4. Synthesis of furanonaphthoquinones with hydroxyamino side chains.

Review 5. Inhibitors of the mitochondrial electron transport chain and de novo pyrimidine biosynthesis as antimalarials: The present status.

Review 6. Malaria.

7. The global distribution of clinical episodes of Plasmodium falciparum malaria.

8. Generation of quinolone antimalarials targeting the Plasmodium falciparum mitochondrial respiratory chain for the treatment and prophylaxis of malaria.

Review 9. Mitochondrial pharmacology.

Review 10. Anti-malarial drugs and the prevention of malaria in the population of malaria endemic areas.

1. Late-Stage C-H Alkylation of Heterocycles and 1,4-Quinones via Oxidative Homolysis of 1,4-Dihydropyridines.

2. Caged Garcinia Xanthones, a Novel Chemical Scaffold with Potent Antimalarial Activity.

3. Synthesis of hydroxycinnamic acid derivatives as mitochondria-targeted antioxidants and cytotoxic agents.

4. Synthesis and Antiplasmodial Activity of 1,2,3-Triazole-Naphthoquinone Conjugates.