Mixed steroidal 1,2,4,5-tetraoxanes: antimalarial and antimycobacterial activity |
| |
Authors: | Solaja Bogdan A Terzi? Natasa Pocsfalvi Gabriella Gerena Lucia Tinant Bernard Opsenica Dejan Milhous Wilbur K |
| |
Institution: | Faculty of Chemistry, University of Belgrade, 11001 Belgrade, Yugoslavia. bsolaja@chem.bg.ac.yu |
| |
Abstract: | Mixed 1,2,4,5-tetraoxanes possessing simple spirocycloalkane and spirocholic acid-derived substituents were prepared and shown to have significantly higher in vitro antimalarial activity than bis-substituted tetraoxanes. Out of 41 synthesized tetraoxanes, 12 were in vitro more potent against Plasmodium falciparum chloroquine-resistant W2 clone than artemisinin, and the most potent one was 2.4 times as active as arteether. In addition, 9 compounds exhibit higher activity than chloroquine against P. falciparum chloroquine-susceptible D6 clone. Cytotoxicity was assessed for most active compounds against the Vero cell line, showing a cytotoxicity/antimalarial potency ratio of 1/(1400-9500). For the first time, tetraoxanes were screened against Mycobacterium tuberculosis with MICs as low as 4.73 microM against H37Rv strain. Mixed tetraoxanes were synthesized in a simple procedure from cholic acid methyl esters by direct coupling of steroidal gem-dihydroperoxide to simple ketones and further transformed into corresponding acids and amides. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|