doi:10.1038/nindia.2016.53 Published online 22 April 2016
Researchers have synthesized several quinoxaline derivatives that inhibit the growth of the human immunodeficiency virus (HIV), which causes acquired immunodeficiency syndrome (AIDS)1. These compounds could be used to develop new anti-HIV drugs for treating AIDS.
Current anti-HIV drugs cause side effects such as rashes and neuropsychiatric disorders. Furthermore, HIV has developed resistance to some existing drugs.
The researchers applied two approaches for designing drugs ― pharmacophore modelling and quantitative structure activity relationships. After virtually screening thousands of compounds in the molecular database of the National Cancer Institute, they designed 32 quinoxaline derivatives.
In common with current anti-HIV drugs, all the compounds interacted with a target viral enzyme. The nitrogen atoms in these compounds were found to bind to a specific amino-acid-containing loop in integrase enzyme, which HIV-1 uses to insert its DNA into the nucleus of a host cell. This is significant as anti-HIV drugs usually inactivate integrase by binding to its specific loop, blocking the transfer of HIV DNA into a host’s cell and thereby preventing the virus from replicating in the host’s body.
Of the 32 compounds, 7 were found to be the potential drug candidates. The researchers further narrowed their search to two compounds that efficiently inhibited the growth of a specific strain of HIV-1. These two compounds were non-toxic and could potentially be developed as HIV inhibitors, the researchers say.
1. Patel, S. B. et al. Design, synthesis and anti-HIV activity of novel quinoxaline derivatives. Eur. J. Med. Chem. (2016) doi:10.1016/j.ejmech.2016.04.019