US Government As Represented by the Secretary of the Army

Wilbur K Milhous

Ai Jeng Lin

Samuel K Martin

Apurba K Bhattacharjee

Dennis E Kyle

Jian Guan

John E VanHamont

Rickey P Hicks

Mark G Hartell

Bruno K Kubata

Daniel L Klayman

Quan Zhang

Bogdan Solaja

Dejan M Opsenica

Gabriella Pocsfalvi

Ayo M Oduola

The invention relates to the treatment of kintoplastid infections by administering a pharmaceutical composition containing an extract from the plant. The invention also relates to isolated, semi-synthetic and synthetic artemisinins that show improved efficacy in treating kinetoplastid infections. This invention also relates to a method of treating kintoplastid infections with artelinic acid and artemisinins and where Artelinic acid is administered orally.

Artemisinins in the clinical and veterinary management of kinetoplastid infections

Disclosed herein are 2-guanidinylimidazolidinedione compounds having the structural formula A or B wherein Rand Rare each independently a hydrogen, halogen, alkyl, alkoxyl, amino, alkylamino or aralkyl, and wherein Ris an alkyl, cycloalkyl, heterocycloalkyl, acyl, aryl, heteroaryl, alkylaryl, sulfonyl, alkylsulfonyl, and pharmaceutically acceptable salts thereof, and methods of making thereof. Also disclosed are methods of treating, preventing, or inhibiting malaria with the 2-guanidinylimidazolidinedione compounds, and pharmaceutical compositions comprising the 2-guanidinylimidazolidinedione compounds, and kits.

2-guanidinylimidazolidinedione compounds and methods of making and using thereof

A stable form of artemisinin wherein an artelinic acid or artesunic acid is complexed with cyclodextrin analogs, preferably, &#x3b2;-cyclodextrin. The complexed cyclodextrin artemisinin formulation shields the peroxide portion of the artemisinin backbone from hydrolytic decomposition rendering it stable in solution. Artelinic acid and cyclodextrin are placed into contact with one another to yield a 2:1 molecular species. Artesunic acid and cyclodextrin yield a 1:1 molecular species. The complexed cyclodextrin artemisinin formulation is effective for the treatment of malaria and is stable in solution for long periods of time.

Artemisinins with improved stability and bioavailability for therapeutic drug development and application

Disclosed herein are mixed steroidal tetraoxanes having the following structural formula 1wherein n is 0, 1, 2, or 3; R is H; ethanoyl, propanoyl, or benzoyl; R1 is H, methyl, ethyl, or isopropyl; R2 is H, methyl, or ethyl; R3 is H, methyl, or ethyl; R4 is H, methyl, ethyl, tert-butyl, phenyl, p-hydroxyphenyl, p-methoxyphenyl, or p-nitrophenyl, orwherein Y is a C-Cstraight or branched-chain alkoxy, orwherein W is N, R5 is hydrogen, methyl, ethyl, n-propyl, isopropyl, or methyl ethanoate 2-yl, and R6 is hydrogen, methyl, ethyl, or n-propyl, or R5 and R6 are part of a pyrrolidine or piperidine ring; X is a C-Cstraight or branched-chain alkoxy, a primary amino, a N-alkylamino wherein the alkyl is a straight-chain alkyl groups containing from 1 to 4 carbon atoms, methyl ethanoate-2-yl, N-phenylamino, p-nitrophenyl, N,N-dimethylamino, N,N-diethylamino, N,N-di(n-propyl)amino, N-pyrrolidino, or N-piperidino as single compounds, and any mixture of all possible stereoisomers at C(4&#x2033;). n may be 0, 1, 2, or 3, and methods of making and using thereof. As disclosed herein, the mixed steroidal tetraoxanes of the present invention exhibit antimalarial, antibacterial, and antiproliferative activity. Thus, as disclosed herein, the mixed steroidal tetraoxanes of the present invention may be used to treat, prevent, or inhibit malaria, bacterial infections, and diseases and disorders associated with cell proliferation in a subject.

Mixed steroidal 1,2,4,5-tetraoxane compounds and methods of making and using thereof

Chemosensitizing agents against chloroquine resistant plasmodium falciparum and methods of making and using thereof

An antimalarial composition contains as the active ingredient a mixture of chemical compound effective in reversing the resistance of cancer cells to chemotherapy drugs and at least one antimalarial agent. A method for treating malaria in mammals comprises administering a composition containing the active ingredient. A method for reducing the resistance of a malarial parasite to an antimalarial agent comprises administering a composition containing the active ingredient.

Antimalarial compositions and methods

This invention relates to novel dihydroartemisinin derivatives, including their pharmaceutically-acceptable salts, which are therapeutically-effective in the pre- and post-treatment of malarial infections.

Novel antimalarial dihydroartemisinin derivatives

Growing community of inventors

Germantown, MD, United States of America

Wilbur K Milhous