title: Synthesis and Inhibiting Activity of Some 4-Hydroxycoumarin Derivatives on HIV-1 Protease.
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 IC(50) = 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.
authors.affiliation: Department of Chemistry, Faculty of Pharmacy, 2 Dunav Street, 1000 Sofia, Bulgaria.
authors.forename: Stancho
authors.initials: S
authors.lastname: Stanchev
authors.forename: Frank
authors.initials: F
authors.lastname: Jensen
authors.forename: Anton
authors.initials: A
authors.lastname: Hinkov
authors.forename: Vasil
authors.initials: V
authors.lastname: Atanasov
authors.forename: Petia
authors.initials: P
authors.lastname: Genova-Kalou
authors.forename: Radka
authors.initials: R
authors.lastname: Argirova
authors.forename: Ilia
authors.initials: I
authors.lastname: Manolov