Stancho Stanchev

Investigation of the antioxidant properties of some new 4-hydroxycoumarin derivatives.

The aim of this investigation was to measure the activity of four 4-hydroxycoumarin derivatives - three of them were described before and one was newly synthesized. The substances were ethyl 2-[(4-hydroxy-2-oxo-2H-chromen-3-yl)(4-hydroxyphenyl)methyl]-3-oxobutanoate (SS-14), 4-[1-(4-hydroxy-2-oxo-2H-chromen-3-yl)-2-(ethoxycarbonyl)-3-oxobutyl]benzoic acid (SS-17), ethyl 2-[(4-hydroxy-2-oxo-2H-chromen-3-yl)(3-nitrophenyl)methyl]-3-oxobutanoate (SS-21) and ethyl 2-[(3,4,5-trimethoxyphenyl)(4-hydroxy-2-oxo-2H-chromen-3-yl)methyl]-3-oxobutanoate (T-2). The synthesis of T-2 consists of two steps. First step was Knoevenagel reaction between 3,4,5-trimethoxybenzaldehyde and ethylacetoacetate. Ethyl 2-(3,4,5-trimethoxy)-phenylmethyleneacetoacetate was the product. Second step was Michael addition reaction between the latter product and 4-hydroxycoumarin. All the compounds were tested in vitro for antioxidant activity in hypochlorous system. The assay was based on the luminol-dependent chemiluminescence of free radicals, which decreased in the presence of 4-hydroxycoumarin derivative. Compound SS-14 (ethyl 2-[(4-hydroxy-2-oxo-2H-chromen-3-yl)(4-hydroxyphenyl)methyl]-3-oxobutanoate) expresses the best scavenger activity at the highest concentration (10(-4)mol/L).

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

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.

Synthesis, Structure and Acid-Base Behaviour of Some 4-Hydroxycoumarin Derivatives

Abstract The compound 3,3′-[(4-hydroxy-3-methoxy-5-nitrophenyl)methylene]-bis(4-hydroxy-2H-1- benzopyran-2-one) (1) crystallizes in the monoclinic system, space group P21/n, with cell constants a = 16.859(4), b = 6.1624(15), c = 25.164(4) Å , β = 98.019(19)°. The two 4-hydroxycoumarin fragments are intramolecularly hydrogen-bonded between hydroxyl and carbonyl groups. The pH-dependent color changes of 4-hydroxycoumarin derivatives were studied by means of potentiometric and spectrophotometric titration. On the basis of the results obtained, the use of 3,3′-[(4-hydroxy-3- methoxy-5-nitrophenyl)methylene]-bis(4-hydroxy-2H-1-benzopyran-2-one) as an indicator in alkalimetry and acidimetry is proposed.