AEGiS-15IAC: A novel synthesis of metalorganic complexes of warfarin (1) and 3,3'-benzylidenebis[4-hydroxycoumarin] (4) and their anti-HIV activity in cell culture (Preliminary report).

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

A novel synthesis of metalorganic complexes of warfarin (1) and 3,3'-benzylidenebis[4-hydroxycoumarin] (4) and their anti-HIV activity in cell culture (Preliminary report).

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. A10265)

Raleva S, Kostova I, Mladenova Z, Froloshka L, Dundarova D, Argirova R
Fac. of Pharmacy, Med. Uni., Sofia, Bulgaria

BACKGROUND: Most of recently reported coumarins with integrase activity showed potent inhibition using isolated enzyme in biochemical assays but this activity has not been proved as antiviral activity in cell culture. Further, the metalorganic complexes of coumarin derivatives with lanthanides showed promising biological effects, but have never been studied for anti-HIV activity.

METHODS: The complexes of Cerium - Ce (III), Lanthanum - La (III) and Neodymum - Nd (III) with (1) and (4) were synthesized and identified by elemental analysis, IR, H, 13C-NMR spectroscopy and mass spectral data. Elemental and mass spectral analyses indicate the formation of compounds corresponding to the compositions Ln(HW)3.4H20, where Ln=Ce, La, Nd; HW= C19H1504. Cytotoxicity, maximal non-toxic concentrations (MNCs) and IC50 were studied on MT-2 cells by neutral red uptake assay. H9/HTLVIIIB cell line was used as a source of HIV-1. Reverse transcriptase (RT) activity of supernatants of HIV-infected MT-2 cells treated/untreated with complexes and ligands was tested by HS-Lenti Kit-RT assay of Cavidi, Sweden. The effect of the compounds was also studied for activity after integration in productively HIV-infected cells.

RESULTS: The preliminary data show lower cytotoxicity of free ligands and La-complexes compared to Ce and Nd ones for both ligands. Free ligands and La complexes had anti-HIV effect (weak anti-RT activity in IC50 concentrations) while Ce and Nd complexes showed such activity in 50 - 100 higher concentrations demonstrated in RT reaction for direct IC50 determination assay.

CONCLUSION: La complexes of (1) and (4) were less cytotoxic compared to Ce and Nd complexes and demonstrated weak anti-RT activity. All ligands and complexes showed no effects on postintegration steps. Further investigations will specify the mechanism and target of anti-HIV action of La complexes of (1) and (4).

Keywords: AEGIS, Acquired Immunodeficiency Syndrome, HIV Seropositivity, Warfarin, HIV-1, RNA-Directed DNA Polymerase, Coumarins, HIV-2, Anticoagulants, Antiviral Agents, Cell Line, Naphthalenesulfonates, Sweden, coumarin, diazonaphthalenedisulfonic acid, organization & administration, methods

040711
A10265