Malaria-infected Mice Are Cured by a Single Oral Dose of New Dimeric Trioxane Sulfones Which Are Also Selectively and Powerfully Cytotoxic to Cancer Cells

Overview

Journal J Med Chem

Publisher American Chemical Society

Specialty Chemistry

Date 2009 Feb 4

PMID 19186946

Citations 22

Authors

Andrew S Rosenthal

Xiaochun Chen

Jun O Liu

Diana C West

Paul J Hergenrother

Theresa A Shapiro

Gary H Posner

Affiliations

Soon will be listed here.

Abstract

A new series of 6 dimeric trioxane sulfones has been prepared from the natural trioxane artemisinin in five or six chemical steps. One of these thermally and hydrolytically stable new chemical entities (4c) completely cured malaria-infected mice via a single oral dose of 144 mg/kg. At a much lower single oral dose of only 54 mg/kg combined with 13 mg/kg of mefloquine hydrochloride, this trioxane dimer 4c as well as its parent trioxane dimer 4b also completely cured malaria-infected mice. Both dimers 4c and 4b were potently and selectively cytotoxic toward five cancer cell lines.

Citing Articles

Evaluation of Chiral Organosulfur Compounds on Their Activity against the Malaria Parasite .

Ngwa C, Stratmann R, Musabyimana J, Pannen K, Schobel J, Frings M Trop Med Infect Dis. 2022; 7(12).

PMID: 36548671 PMC: 9785921. DOI: 10.3390/tropicalmed7120416.

Chloroaluminate Ionic Liquid Immobilized on Magnetic Nanoparticles as a Heterogeneous Lewis Acidic Catalyst for the Friedel-Crafts Sulfonylation of Aromatic Compounds.

Nguyen N, Nguyen Q, Le T, Luu T, Tran K, Pham P Molecules. 2022; 27(5).

PMID: 35268745 PMC: 8911771. DOI: 10.3390/molecules27051644.

Peroxides with Anthelmintic, Antiprotozoal, Fungicidal and Antiviral Bioactivity: Properties, Synthesis and Reactions.

A Vil V, Yaremenko I, Ilovaisky A, Terentev A Molecules. 2017; 22(11).

PMID: 29099089 PMC: 6150334. DOI: 10.3390/molecules22111881.

Malaria-Infected Mice Are Cured by a Single Low Dose of a New Silylamide Trioxane Plus Mefloquine.

Woodard L, Mott B, Singhal V, Kumar N, Shapiro T, Posner G Pharmaceuticals (Basel). 2016; 2(3):228-235.

PMID: 27713236 PMC: 3978545. DOI: 10.3390/ph2030228.

Development of Anticancer Agents from Plant-Derived Sesquiterpene Lactones.

Ren Y, Yu J, Kinghorn A Curr Med Chem. 2016; 23(23):2397-420.

PMID: 27160533 PMC: 5012922. DOI: 10.2174/0929867323666160510123255.

References

Myint H, Ashley E, Day N, Nosten F, White N . Efficacy and safety of dihydroartemisinin-piperaquine. Trans R Soc Trop Med Hyg. 2007; 101(9):858-66. DOI: 10.1016/j.trstmh.2007.05.018. View

Begue J, Bonnet-Delpon D . Fluoroartemisinins: metabolically more stable antimalarial artemisinin derivatives. ChemMedChem. 2007; 2(5):608-24. DOI: 10.1002/cmdc.200600156. View

Ekthawatchai S, Kamchonwongpaisan S, Kongsaeree P, Tarnchompoo B, Thebtaranonth Y, Yuthavong Y . C-16 artemisinin derivatives and their antimalarial and cytotoxic activities: syntheses of artemisinin monomers, dimers, trimers, and tetramers by nucleophilic additions to artemisitene. J Med Chem. 2001; 44(26):4688-95. DOI: 10.1021/jm0103007. View

Alagbala A, McRiner A, Borstnik K, Labonte T, Chang W, DAngelo J . Biological mechanisms of action of novel C-10 non-acetal trioxane dimers in prostate cancer cell lines. J Med Chem. 2006; 49(26):7836-42. PMC: 5545891. DOI: 10.1021/jm060803i. View

Snow R, Guerra C, Noor A, Myint H, Hay S . The global distribution of clinical episodes of Plasmodium falciparum malaria. Nature. 2005; 434(7030):214-7. PMC: 3128492. DOI: 10.1038/nature03342. View

Breman J, Alilio M, Mills A . Conquering the intolerable burden of malaria: what's new, what's needed: a summary. Am J Trop Med Hyg. 2004; 71(2 Suppl):1-15. View

Harris K, Harney E, Small E . Liposomal doxorubicin for the treatment of hormone-refractory prostate cancer. Clin Prostate Cancer. 2004; 1(1):37-41. DOI: 10.3816/cgc.2002.n.005. View

Efferth T . Mechanistic perspectives for 1,2,4-trioxanes in anti-cancer therapy. Drug Resist Updat. 2005; 8(1-2):85-97. DOI: 10.1016/j.drup.2005.04.003. View

Troye-Blomberg M, Berzins K . Immune interactions in malaria co-infections with other endemic infectious diseases: implications for the development of improved disease interventions. Microbes Infect. 2008; 10(9):948-52. DOI: 10.1016/j.micinf.2008.07.014. View

10.

Sagara I, Diallo A, Kone M, Coulibaly M, Diawara S, Guindo O . A randomized trial of artesunate-mefloquine versus artemether-lumefantrine for treatment of uncomplicated Plasmodium falciparum malaria in Mali. Am J Trop Med Hyg. 2008; 79(5):655-61. View

11.

Jefford C . Synthetic peroxides as antimalarials. Curr Opin Investig Drugs. 2004; 5(8):866-72. View

12.

Adjuik M, Babiker A, Garner P, Olliaro P, Taylor W, White N . Artesunate combinations for treatment of malaria: meta-analysis. Lancet. 2004; 363(9402):9-17. DOI: 10.1016/s0140-6736(03)15162-8. View

13.

Ashley E, White N . Artemisinin-based combinations. Curr Opin Infect Dis. 2005; 18(6):531-6. DOI: 10.1097/01.qco.0000186848.46417.6c. View

14.

Takara K, Sakaeda T, Yagami T, Kobayashi H, Ohmoto N, Horinouchi M . Cytotoxic effects of 27 anticancer drugs in HeLa and MDR1-overexpressing derivative cell lines. Biol Pharm Bull. 2002; 25(6):771-8. DOI: 10.1248/bpb.25.771. View

15.

Guthmann J, Cohuet S, Rigutto C, Fortes F, Saraiva N, Kiguli J . High efficacy of two artemisinin-based combinations (artesunate + amodiaquine and artemether + lumefantrine) in Caala, Central Angola. Am J Trop Med Hyg. 2006; 75(1):143-5. View

16.

Zhou H, Wang Z, Li A . Dihydroartemisinin induces apoptosis in human leukemia cells HL60 via downregulation of transferrin receptor expression. Anticancer Drugs. 2008; 19(3):247-55. DOI: 10.1097/cad.0b013e3282f3f152. View

17.

Posner G, Paik I, Chang W, Borstnik K, Sinishtaj S, Rosenthal A . Malaria-infected mice are cured by a single dose of novel artemisinin derivatives. J Med Chem. 2007; 50(10):2516-9. DOI: 10.1021/jm070149m. View

18.

Gatter K, Brown G, Trowbridge I, Woolston R, Mason D . Transferrin receptors in human tissues: their distribution and possible clinical relevance. J Clin Pathol. 1983; 36(5):539-45. PMC: 498283. DOI: 10.1136/jcp.36.5.539. View

19.

Posner G, Maxwell J, ODowd H, Krasavin M, Xie S, Shapiro T . Antimalarial sulfide, sulfone, and sulfonamide trioxanes. Bioorg Med Chem. 2000; 8(6):1361-70. DOI: 10.1016/s0968-0896(00)00079-1. View

20.

Posner G, ODowd H, Ploypradith P, Cumming J, Xie S, Shapiro T . Antimalarial cyclic peroxy ketals. J Med Chem. 1998; 41(12):2164-7. DOI: 10.1021/jm980088f. View