Ionic liquids: Potential inhibitors of HIV-1 integrase

ORGN 289

Sanjay V. Malhotra, malhotrasa@mail.nih.gov1, Yves Pommier, pommier@mail.nih.gov2, Vineet Kumar, kumarvin@mail.nih.gov1, Kasthuraiah Maddali2, Christophe Marchand2, Anu Puri3, and Amichai Yavlovich3. (1) Laboratory of Synthetic Chemistry, National Cancer Institute - Frederick, SAIC-Frederick, 1050 Boyles Street, Frederick, MD 21702, (2) Laboratory of Molecular Pharmacology, CCR, NCI, NIH, Bethesda, MD 20892, (3) Membrane Structure and Function Section, National Cancer Institute - Frederick, Center for Cancer Research Nanobiology Program, Frederick, MD 21702
The ‘designer' aspect of ionic liquids (ILs) renders the possibilities for preparation of compounds with ‘tunable' physiochemical properties and toxicity. As a result ILs are appealing materials for drug development and therapeutics. An understanding of their toxicity (cell & animal) and physiochemical properties (e.g. hydrophilicity and lipophilicity) is necessary in selection and ‘design' of ILs in relation to specific therapeutic application. Here we implemented this approach through toxicity studies using CD-1 mice on a wide range of ionic liquids. Investigation of their inhibitory effect on HIV-1 integrase activity, revealed that depending on their physiochemical properties these compounds could affect the growth of HIV. Biophysical analysis showed correlation between the cation structure and integrase inhibition. Thus, our studies for the first time illustrate the possibilities in clinical application of ionic liquids.
 

Heterocycles and Aromatics
1:00 PM-5:20 PM, Monday, August 17, 2009 Walter E. Washington Convention Center -- 206, Oral

Division of Organic Chemistry

The 238th ACS National Meeting, Washington, DC, August 16-20, 2009