Table of Contents
ISRN Pharmaceutics
Volume 2011, Article ID 137637, 9 pages
http://dx.doi.org/10.5402/2011/137637
Research Article

Synthesis and Inhibiting Activity of Some 4-Hydroxycoumarin Derivatives on HIV-1 Protease

1Department of Chemistry, Faculty of Pharmacy, 2 Dunav Street, 1000 Sofia, Bulgaria
2Department of Chemistry, Faculty of Science, University of Aarhus, Langelandsgade 140, 8000 Aarhus C, Denmark
3Laboratory of Virology, Faculty of Biology, Sofia University “St. Kliment Ohridski”, 8 Dragan Zankov, 1164 Sofia, Bulgaria
4Laboratory of Biocoordination and Bioanalytical Chemistry, Faculty of Chemistry, Sofia University “St. Kliment Ohridski”, 1 J. Bourchier, 1164 Sofia, Bulgaria
5Laboratory of Cell Cultures, National Center of Infectious and Parasitic Diseases, 44 A Stoletov Street, 1233 Sofia, Bulgaria
6Laboratory of Retroviruses, National Center of Infectious and Parasitic Diseases, 44 A Stoletov Street, 1233 Sofia, Bulgaria
7Department of Pharmaceutical Chemistry, Faculty of Pharmacy, 2 Dunav Street, 1000 Sofia, Bulgaria

Received 11 April 2011; Accepted 14 May 2011

Academic Editors: R. Cao, F. Fullas, P.-W. Hsieh, and S. Raic-Malic

Copyright © 2011 Stancho Stanchev et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Six novel 4-hydroxycoumarin derivatives were rationally synthesized, verified, and characterized by molecular docking using crystal HIV-1 protease. Molecular docking studies predicted antiprotease activity of (7) and (10). The most significant functional groups, responsible for the interaction with HIV-1 protease by hydrogen bonds formation are pyran oxygen, atom, lactone carbonyl oxygen and one of the hydroxyl groups. The newly synthesized compounds were biologically tested in MT-4 cells for inhibiting HIV-1 replication, exploring the protection of cells from the cytopathic effect of HIV measured by cell survival in MTT test. One derivative −7 showed 76–78% inhibition of virus infectivity with IC50 = 0.01 nM, much less than the maximal nontoxic concentration (1 mM). Antiprotease activity of 7 in two different concentrations was detected to be 25%. Nevertheless, the results of study of (7) encourage using it as a pharmacophore for further synthesis and evaluation of anti-HIV activity.