Scientific Publications-2006-HAT

2006

New Azasterols against Trypanosoma brucei: Role of 24-Sterol Methyltransferase in Inhibitor Action by Gros L, Castillo-Acosta VM, Jimenez Jimenez C, Sealey-Cardona M, Vargas S, Manuel Estevez A, Yardley V, Rattray L, Croft SL, Ruiz-Perez LM, Urbina JA, Gilbert IH, Gonzalez-Pacanowska D. Antimicrob Agents Chemother. 2006 Aug; 50(8):2595-601.
A series of azasterol derivatives, designed as potential inhibitors of the Δ24 –sterol methyltransferase enzyme (24-SMT), were synthesized and evaluated for their activities against parasitic protozoa. We conclude that the designed compounds act at sites other than 24-SMT in Trypanosoma brucei.
Click here to download the full article [PDF]

Aziridine-2,3-dicarboxylate inhibitors targeting the major cysteine protease of Trypanosoma brucei as lead trypanocidal agents by Vicik R, Hoerr V, Glaser M, Schultheis M, Hansell E, McKerrow JH, Holzgrabe U, Caffrey CR, Ponte-Sucre A, Moll H, Stich A, Schirmeister T. Bioorg. Med. Chem. Lett. 2006 May 15;16(10):2753-7. Epub 2006 Mar 3.
The protozoan parasite Trypanosoma brucei causes Human African trypanosomiasis, which is fatal if left untreated. Due to the toxicity of currently used drugs and emerging drug resistance, there is an urgent need for novel therapies. The major trypanosome papain-like cysteine protease expressed by the parasite (e.g., rhodesain in T. b. rhodesiense) is considered an important target for the development of new trypanocidal drugs.
Click here to download the full article [PDF]

Discovery of Trypanocidal Compounds by Whole Cell HTS of Trypanosoma brucei by Mackey ZB, Baca AM, Mallari JP, Apsel B, Shelat A, Hansell EJ, Chiang PK, Wolff B, Guy KR, Williams J, McKerrow JH. Chem Biol Drug Des. 2006 May;67(5):355-63.
One potentially rapid and cost-effective approach to identifying and developing new trypanocidal drugs would be high throughput-screening of existing drugs already approved for other uses, as well as clinical candidates in late development. A screen was performed in a collection of 2160 FDA approved drugs, bioactive compounds and natural products to identify hits that were cytotoxic to cultured Trypanosoma brucei at a concentration of 1lM or less. From the screen, 35 hits from seven different drug categories were identified.
Click here to download the full article [PDF]