Orally active, antimalarial, anticancer, artemisinin-derived trioxane dimers with high stability and efficacy

Journal of Medicinal Chemistry

Volumn 46, Issue 6, 2003, Pages 1060-1065

  Posner, Gary H ^a,c   Paik, Ik Hyeon ^a,c   Sur, Surojit ^a,c   McRiner, Andrew J ^a,c   Borstnik, Kristina ^a,c   Xie, Suji ^b,c   Shapiro, Theresa A ^b,c  

^a JOHNS HOPKINS UNIVERSITY   (United States)

^b JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c JOHNS HOPKINS BLOOMBERG SCHOOL OF PUBLIC HEALTH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIMALARIAL AGENT; ANTINEOPLASTIC AGENT; ARTELINIC ACID; ARTEMISININ DERIVATIVE; ARTESUNATE; TRIOXANE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CANCER CELL CULTURE; CANCER INHIBITION; CONTROLLED STUDY; CYTOTOXICITY; DRUG EFFICACY; DRUG STABILITY; DRUG STRUCTURE; HUMAN; HUMAN CELL; NONHUMAN; RAT; STRUCTURE ANALYSIS; THERMOSTABILITY;

ADMINISTRATION, ORAL; ANIMALS; ANTIMALARIALS; ANTINEOPLASTIC AGENTS; ARTEMISININS; DRUG SCREENING ASSAYS, ANTITUMOR; HUMANS; MALARIA; MICE; PLASMODIUM BERGHEI; PLASMODIUM FALCIPARUM; POLYMERS; SOLUBILITY; STRUCTURE-ACTIVITY RELATIONSHIP; TUMOR CELLS, CULTURED; WATER;

EID: 0037435053     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm020461q     Document Type: Article

References (35)

1. Beekman, A. C.; Barenstsen, A. R. W.; Woerdenbag, H. J.; Van Uden, W.; Pras, N. Stereochemistry- Dependent Cytotoxicity of Some Artemisinin Derivatives. J. Nat. Prod. 1997, 60, 325-330.
2. Galal, A. M.; Ahmad, M. S.; El-Feraly, F. S. Preparation and Characterization of a New Artemisinin-Derived Dimer. J. Nat. Prod. 1996, 59, 917-920.
3. Venugopalan, B.; Bapat, C. P.; Karnik, P. J.; Catterjee, D. K.; Iyer, N.; Lepcha, D. Antimalarial Activity of Novel Ring- Contracted Artemisinin Derivatives. J. Med. Chem. 1995, 38, 1922-1927.
4. Posner, G. H.; Ploypradith, P.; Hapangama, W.; Wang, D.; Cumming, J. N.; Dolan, P.; Kensler, T. W.; Klinedinst, D.; Shapiro, T. A.; Zheng, Q. Y.; Murray, C. K.; Pilkington, L. G.; Jayasinghe, L. R.; Bray, J. F.; Daughenbaugh, R. Trioxane Dimers Have Potent Antimalarial, Antiproliferative, and Antitumor Activities in Vitro. Bioorg. Med. Chem. 1997, 5, 1257-1265.
5. Posner, G. H.; Northrop, J.; Paik, I.-H.; Borstnik, K.; Dolan, P.; Kensler, T. W.; Xie, S.; Shapiro, T. A. New Chemical and Biological Aspects of Artemisinin-Derived Trioxane Dimers. Bioorg. Med. Chem. 2002, 10, 227-232.
6. Posner, G. H.; Ploypradith, P.; Parker, M. H.; O'Dowd, H.; Woo, S.-H.; Northrop, J.; Krasavin, M.; Dolan, P.; Kensler, T. W.; Xie, S.; Shapiro, T. A. Antimalarial, Antiproliferative, and Antitumor Activities of Artemisinin-Derived, Chemically Robust, Trioxane Dimers. J. Med. Chem. 1999, 42, 4275-4280.
7. Jung, M.; Lee, S. Stability of Acetal and Non-Acetal Type Analogs of Artemisinin in Simulated Stomach Acid. Bioorg. Med. Chem. Lett. 1998, 8, 1003-1006.
8. Aboubdellah, A.; Bégué, J.-P.; Bonnet-Delpon, D.; Gontier, J.-C.; Nga, T. T.; Thac, T. D. Synthesis and in Vivo Antimalarial Activity of 12α-Trifluoromethyl-hydroartemisinin. Bioorg. Med. Chem. Lett. 1996, 6, 2717-2720.
9. Pu, Y. M.; Ziffer, H. Synthesis and Antimalarial Activities of 12β-Allyldeoxoartemisinin. J. Med. Chem. 1995, 38, 613-616.
10. Vroman, J. A.; Khan, I. A.; Avery, M. A. Copper(I)-Catalyzed Conjugate Addition of Grignard Reagents to Acrylic Acids: Homologation of Artemisinic Acid and Subsequent Conversion to 9-Substituted Artemisinin Analogs. Tetrahedron Lett. 1997, 38, 6173-6176.
11. Avery, M. A.; Alvim-Gaston, M.; Woolfrey, J. R. Synthesis and Structure-Activity Relationships of Peroxidic Antimalarials Based on Artemisinin. Adv. Med. Chem. 1999, 4, 125-217.
12. Jung, M.; Lee, S. Synthesis and Cytotoxicity of Novel Artemisinin Analogs. Bioorg. Med. Chem. Lett. 1997, 7, 1091-1094.
13. Haynes, R. K.; Vonwiller, S. C. Efficient Preparation of Novel Qinghaosu (Artemisinin) Derivatives. Synlett 1992, 481-483.
14. Woo, S. H.; Parker, M. H.; Ploypradith, P.; Northrop, J.; Posner, G. H. Direct Conversion of Anomeric OH → F → R in the Artemisinin Family of Antimalarial Trioxanes. Tetrahedron Lett. 1998, 39, 1533-1536.
15. Posner, G. H.; Parker, M. H.; Northrop, J.; Elias, J. S.; Ploypradith, P.; Xie, S.; Shapiro, T. A. Orally Active, Hydrolytically Stable, Semisynthetic, Antimalarial Trioxanes in the Artemisinin Family. J. Med. Chem. 1999, 42, 300-304.
16. O'Dowd, H.; Ploypradith, P.; Xie, S.; Shapiro, T. A.; Posner, G. H. Antimalarial Artemisinin Analogs. Synthesis via Chemoselective C-C Bond Formation and Preliminary Biological Evaluation. Tetrahedron 1999, 55, 3625-3636.
17. O'Neill, P. M.; Searle, N. L.; Kan, K.-W.; Storr, R. C.; Maggs, J. L.; Ward, S. A.; Raynes, K.; Park, B. K. Novel, Potent, Semisynthetic Antimalarial Carba Analogues of the First-Generation 1,2,4-Trioxane Artemether. J. Med. Chem. 1999, 42, 5487-5493.
18. O'Neill, P. M.; Pugh, M.; Stachulski, A. V.; Ward, S. A.; Davies, J.; Park, B. K. Optimisation of the Allylsilane Approach to C-10 Deoxo Carba Analogues of Dihydroartemisinin: Synthesis and in Vitro Antimalarial Activity of New, Metabolically Stable C-10 Analogues. J. Chem. Soc., Perkin Trans. 1 2001, 2682-2689.
19. Rychnovsky, S. D.; Fryszman, O.; Khire, U. R. Convergent Synthesis of a Polyol Chain with 4-Acetoxy-1,3-dioxanes Using a 1,1-Bis((trimethylsilyl)methyl)ethene Linchpin. Tetrahedron Lett. 1999, 40, 41-44.
20. Ma, J.; Katz, E.; Ziffer, H. A New Synthetic Route to 10β-Alkyldeoxoartemisinins. Tetrahedron Lett. 1999, 40, 8543-8545.
21. Jung, M.; Lee, S. A Concise Synthesis of Novel Aromatic Analogs of Artemisinin. Heterocycles 1997, 45, 1055-1058.
22. Adam, W.; Hert, M. Reactions of 1,2-Dioxetanes with Heteroatom Nucleophiles: Adduct Formation by Nucleophilic Attack at the Peroxide Bond. J. Am. Chem. Soc. 1992, 114, 5591-5598.
23. O'Dowd, H.; Ploypradith, P.; Xie, S.; Shapiro, T. A.; Posner, G. H. Antimalarial Artemisinin Analogs. Synthesis via Chemoselective C-C Bond Formation and Preliminary Biological Evaluation. Tetrahedron 1999, 55, 3625-3636.
24. Posner, G. H.; Roger, D. Z. Organic Reactions at Alumina Surfaces. Mild and Selective Opening of Epoxides by Alcohols, Thiols, Benzeneselenols, Amines, and Acetic Acid. J. Am. Chem. Soc. 1977, 99, 8208-8213.
25. Li, Q.-G.; Peggins, J. O.; Lin, A. J.; Masonic, K. J.; Troutman, K. M.; Brewer, T. G. Pharmacology and Toxicology of Artelinic Acid: Preclinical Investigations on Pharmacokinetics, Metabolism, Protein and Red Blood Cell Binding, and Acute and Anorectic Toxicities. Trans. R. Soc. Trop. Med. Hyg. 1998, 92, 332-340.
26. For experimental details of the testing protocol, including references to development of the assay, see the following. Posner, G. H.; González, L.; Cumming, J. N.; Klinedinst, D.; Shapiro, T. A. Synthesis and Antimalarial Activity of Heteroatom-Containing Bicyclic Endopeoxides. Tetrahedron 1997, 53, 37-50.
27. Peters, W.; Robinson, B. L.; Rossiter, J. C.; Jefford, C. W. The Chemotherapy of Rodent Malaria. XLVIII. The Activities of Some Synthetic 1,2,4-Trioxanes against Chloroquine-Sensitive and Chloroquine-Resistant Parasites. Part 1: Studies Leading to the Development of Novel cis-Fused Cyclopenteno Derivatives. Ann. Trop. Med. Parasitol. 1993, 87, 1-7.
28. Boyd, M. R.; Paull, K. D. Some Practical Considerations and Applications of the National Cancer Institute in Vitro Anticancer Drug Discovery Screen. Drug Dev. Res. 1995, 34, 91-109.
29. Robert, A.; Dechy-Cabaret, O.; Cazelles, J.; Meunier, B. From Mechanistic Studies on Artemisinin Derivatives to New Modular Antimalarial Drugs. Acc. Chem. Res. 2002, 35, 167-174.
30. Jung, M.; Lee, K.; Kendrick, H.; Robinson, B. L.; Croft, S. L. Synthesis, Stability, and Antimalarial Activity of New Hydrolytically Stable and Water-Soluble (+)-Deoxoartelinic Acid. J. Med. Chem. 2002, 45, 4940-4944.
31. Avery, M. A.; Alvim-Gaston, M.; Vroman, J. A.; Wu, B.; Ager, A.; Peters, W.; Robinson, B. L.; Charman, W. Structure-Activity Relationships of the Antimalarial Agent Artemisinin. 7. Direct Modification of (+)-Artemisinin and in Vivo Antimalarial Screening of New, Potential Preclinical Antimalarial Candidates. J. Med. Chem. 2002, 45, 4321-4335.
32. Borstnik, K.; Paik, I.-H.; Posner, G. H. Malaria: New Chemotherapeutic Peroxide Drugs. Mini-Rev. Med. Chem. 2002, 2, 573-583.
33. Ma, J.; Katz, E.; Kyle, D. E.; Ziffer, H. Syntheses and Antimalarial Activities of 10-Substituted Deoxoartemisinins. J. Med. Chem. 2000, 43, 4228-4232.
34. Haynes, R. K.; Chan, H.-W.; Cheung, M.-K.; Lam, W.-L.; Soo, M.-K.; Tsang, H.-W.; Voerste, A.; Willians, I. D. C-10 Ester and Ether Derivatives of Dihydroartemisinin - 10-α Artesunate, Preparation of Authentic 10-β Artesunate, and of Other Ester and Ether Derivatives Bearing Potential Intercalating Groups at C-10. Eur. J. Org. Chem. 2002, 113-132.
35. Rodriguez, C. M.; Ode, J. M.; Palazon, J. M.; Martin, V. S. Simple and Efficient Oxidation of Sulfides to Sulfones Using Catalytic Ruthenium Tetroxide. Tetrahedron 1992, 48, 3571-3576.