Bioinorganic Chemistry and Applications
Volume 2006 (2006), Article ID 71938, 7 pages
doi:10.1155/BCA/2006/71938

Antihuman Immunodeficiency Virus Type 1 (HIV-1) Activity of Rare Earth Metal Complexes of 4-Hydroxycoumarins in Cell Culture

Ilia Manolov,1 Sevda Raleva,2 Petya Genova,2 Alexey Savov,3 Liliana Froloshka,2 Daniela Dundarova,2 and Radka Argirova2

1Department of Organic Chemistry, Faculty of Pharmacy, Medical University, 2 Dunav Street, Sofia 1000, Bulgaria
2Department of Virology, National Center of Infectious and Parasitic Diseases, 44A Stoletov Street, Sofia 1233, Bulgaria
3Laboratory of Molecular Pathology, Medical University, 2 Zdrave Street, Sofia 1606, Bulgaria

Received 23 December 2004; Revised 9 March 2005; Accepted 17 June 2005

Copyright © 2006 Ilia Manolov 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

The cerium Ce(III), lanthanum La(III), and neodymium Nd(III) complexes with 4-hydroxy-3-(3-oxo-1-phenylbutyl)-2H-1-benzopyran-2-one (warfarin) (W) and 3,3′-benzylidenebis[4-hydroxycoumarin] (1) were synthesized and studied for the first time for cytotoxicity (on MT-2 cells) and as anti-HIV agents under acute and chronic infection. The complexes were characterized by different physicochemical methods: mass spectrometry, ¹H NMR, ¹³C NMR, and IR spectroscopy. The spectra of the complexes were interpreted on the basis of comparison with the spectrum of the free ligands. Anti-HIV effect of the complexes/ligands was measured in MT-2 cells by microtiter infection assay. Detection of endogenous reverse transcriptase (RT) activity and RT processivity by PCR indicative for proviral DNA synthesis demonstrated that anti-HIV activity has not been linked to early stages of viral replication. No effect on late steps of viral replication has been found using cells chronically producing HIV-1LAI virus. La(W) demonstrated anti-HIV activity (IC50=21.4μM) close to maximal nontoxic concentration. Nd(W), Ce(1), and Nd(1) demonstrated limited anti-HIV potency, so none of the complexes seems appropriate to be used in clinic. Further targeting of HIV-1 inhibition by La(W) is under progress.