title: Antihuman Immunodeficiency Virus Type 1 (HIV-1) Activity of Rare Earth Metal Complexes of 4-Hydroxycoumarins in Cell Culture.
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, (1)H NMR, (13)C 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-1(LAI) virus. La(W) demonstrated anti-HIV activity (IC50=21.4 muM) 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.
authors.affiliation: Department of Organic Chemistry, Faculty of Pharmacy, Medical University, 2 Dunav Street, 1000 Sofia, Bulgaria.
authors.forename: Ilia
authors.initials: I
authors.lastname: Manolov
authors.forename: Sevda
authors.initials: S
authors.lastname: Raleva
authors.forename: Petya
authors.initials: P
authors.lastname: Genova
authors.forename: Alexey
authors.initials: A
authors.lastname: Savov
authors.forename: Liliana
authors.initials: L
authors.lastname: Froloshka
authors.forename: Daniela
authors.initials: D
authors.lastname: Dundarova
authors.forename: Radka
authors.initials: R
authors.lastname: Argirova