The synthesis and antimicrobial activity of some 4-hydroxycoumarin derivatives.

Due to exceptional reactivity of 4-hydroxycoumarin, the synthesis of new coumarin derivatives of dimer and tetramer type has been carried out. The synthesis was carried out from 4-hydroxycoumarin and various aromatic aldehydes. In this way, compounds of the dimer 3,3'-(benzilidene)bis (4-hydroxycoumarin) type, as well as of the tetramer 3,3',3'',3'''-(1,4-dimethylenphenyl)tetra (4-hydroxycoumarin) type were prepared. The newly synthesized derivatives contain different functional groups, and as such they could exhibit microbiological activity. Therefore, we tested the microbiological activity of these derivatives on various species of bacteria and fungi. The tested compounds have shown different activity in terms of growth inhibition of microorganisms. Newly synthesized derivatives exhibit antibacterial activities, manifested as growth inhibition on Gram-positive bacteria types (Bacillus, Staphylococcus), while the activity against Candida was much weaker. The same compound did not show any antimicrobial activity against two Gram-negative bacteria types (Escherichia coli, Pseudomonas aeruginosa). The compound 1 showed the best microbiological activity. The obtained results confirmed its good antibacterial and antimycotic activities against different microorganisms.

[Antidepressives and antidepressive interactions with other drugs]. / Antidepresivi i interakcije antidepresiva s drugim lijekovima.

During the therapy with antidepressive agents, for the reason of its duration, numerous drug-drug interactions may occur. Antidepressive agents inhibit P450 enzyme activity and interfere with other drug metabolism. Many interactions are acceptable from the clinical point of view, and some are seriously dangerous indicating a need for their better knowledge. The aim of this work is to point out the possible interactions between antidepressive agents and other drugs.

The 4-arylaminocoumarin derivatives log P values calculated according to Rekker's method.

In the QSAR (quantitative structure-activity relationship) and QSPR (quantitative structure-property-activity relationship) study physico-chemical property, lipophilicity is used, to predict bioactivity of the newly synthesized coumarin compounds. Lipophilicity is a property of a molecule which depends on and can be changed by modifications in molecular structure. The parameter of the lipophilicity, partition coefficient (log P), is commonly used in drug designing and it is a numeric characteristic of lipophilicity of the examined substance, potential drug. The synthesis of 4-arylaminocoumarins derivatives from 4-hydroxycoumarin, has been carried out. In this work we described the fragmental method of calculation of partition coefficient according to the Rekker's method, because the best correlation between calculated and experimental values log P was determined according to the Rekker model. 4-Arylaminocoumarin has negative value of log P, but substitution with alkyl or allyl groups on the position 3 increases lipofilicity. Introduction of methyl or ethyl group into position 3 increases lipofilicity, suggesting that by increasing the chain length the values of log P become higher. The influence of allyl substituent in position three increases lipophilicity similar to methyl group. The aryl supstitent decreases lipoflicity, but a general relationship among them could not be established. The results obtained in this study enable further synthesis of new coumarin derivatives and predict their biological activity and properties.

QSAR and QSPR study of derivatives 4-arylaminocoumarin.

Coumarin and its derivatives are reactive compounds, suitable for many syntheses. They are used as anticoagulants, antibacterial, animistic compounds. The interest in coumarins has increased because it was found that they reduce the HIV virus activity. The synthesis of 4-arylaminocoumarin derivatives from 4-hydroxycoumarin, has been carried out, and their antimycotic effects were tested. In the QSAR (quantitative structure-activity relationship) QSPR (quantitative structure-property-activity relationship) study we have used physicochemical properties and topological indices (Balaban index J(G), Wiener index W(G), information-theoretical index I(G), and valence connectivity index (G), to predict bioactivity of the newly synthesized coumarin compounds. By using methods of molecular modelling, the relationships between structure, properties and activity of coumarin compounds have been investigated. The best QSPR models were obtained using valence connectivity index or combination indices. According Rekker's method the best correlation of calculated values log P, has been obtained with the model based on the inhibition zone (I) 4-arylaminocoumarin derivatives expressed in mm. The results obtained in this study enable further synthesis of new coumarin derivatives and predict their biological activity and properties.