Four 4-hydroxycoumarin derivatives were synthesized and the structure was confirmed by NMR spectroscopy and Mass spectrometry. Tested compounds have shown significant antimicrobial activity against Bacillus subtilis subsp. spizizenii, Bacillus cereus, Staphylococcus aureus, and Staphylococcus epidermidis, and the effect of more halogens on the benzene nucleus, as well as the combination of halogen and alkyl groups, on the antimicrobial activity, was investigated. According to the docking study, these compounds can operate simultaneously on two enzymes, amylase and gyrase (1BAG and 1KZN), which are known to play an important role in bacterial life. Obtained docking study parameters for tested compounds showed an association with the in vitro results of the antimicrobial activity of these compounds. In silico tests of molecular properties of the tested compounds showed that the compounds met Lipinski's rule of five. In this paper, the ADME parameters of tested compounds were also calculated: Caco2 (in vitro Caco2 cell permeability), HIA (human intestinal absorption), MDCK (in vitro Mandin Darby Canine Kidney (MDCK) cell permeability), TPSA (topological polar surface area), etc.

In the present investigation, a series of coumarin-based compounds containing a chalcone moiety were studied for their in vitro and in silico pro- perties. The DFT global chemical reactivity descriptors (chemical hardness, total energy, electronic chemical potential and electrophilicity) were calculated for four synthesized compounds and used to predict their relative stability and reactivity. The antibacterial activities of all compounds were screened against Bacillus subtilis (ATCC 6633) and Bacillus cereus (ATCC 11778). The quantum-chemical calculations indicated that the antibacterial activity correlates well with chemical reactivity descriptors of the molecules.

Objective: As a further part of our chemical and biological studies in this field, we describe the preparations of the properly substituted benzylidene-bis-(4-hydroxycoumarin) derivatives 5a-h and 3-(6-oxo-(1H)-benzopyrano[4,3-b]benzopyran-7-yl)-4-hydroxycoumarin derivatives 6a-e . Methods: The synthesized compounds were screened for their in vitro antimicrobial activity against five strains of bacteria and two fungal strains using disk diffusion assay and dilution method. The way in which the substituent group’s physicochemical properties influence the antimicrobial activity is discussed in the paper. Results: The in vitro evaluation of their inhibitory properties towards five strains of Gram-positive and Gram-negative bacteria and two fungal strains indicated that the                                       4-trifluoromethylbenzylidene derivative of bis-(4-hydroxycoumarin) (compound 5c ) and                    3-(6-oxo-(1 H )-18-bromobenzopyrano[4,3-b]benzopyran-7-yl)-4-hydroxycoumarin derivative (compound 6b ) possess the most potent antibacterial activities, with MIC of 3.9 μg/mL - 7.8 μg/mL against Gram-positive bacteria. Conclusion: The compound 6b has greater antibacterial activity than the standard chloramfenicol (inhibition zone 26 mm and MIC 1.9 μg/mL) against Staphyloccocus aureus and could be considered as leading compound in the future antimicrobial drug development. Key words: Benzylidene-bis-(4-hydroxycoumarin), benzopyranocoumarin derivatives, antibacterial assays , antifungal activity.

Background and purpose: Having in mind the results of our previous work, which suggested antimicrobial activity of some 3-cynnamoyl-4-hydroxycoumarins, we carried out the synthesis of several new derivatives of this group. The microbiological activity of compounds was tested by the diffusion and dilution methods on various species of bacteria. The aim of the study was to evaluate the influence of the substituents on antimicrobial activity. Material and methods: A series of new 3-cynnamoyl-4-hydroxycoumarins was prepared by the reaction of nucleophylic addition from 3-acetyl-4-hydroxycoumarin acting on appropriate aromatic aldehydes. The microbiological activity of compounds was tested by the diffusion and dilution methods on species of bacteria Pseudomonas aeruginosa, Echerichia coli, Salmonella typhimurium, Bordatella bronchiseptica, Bacillus subtilis, and Staphyloccocus aureus. Results: The synthesis of new 3-cynnamoyl-4-hydroxycoumarins was carried out. The elementary content of the synthesized compounds was confirmed by elementary analysis, and structures were confirmed with IR-spectrophotometry and 1 H-NMR spectrophotometry.

Anticoagulant therapy is most commonly assessed by measuring the effect of the drug on global clotting assay, such as APTT. It is known that response of the APTT to heparin may be decreased in patients with high levels of factor VIII. In this work, we have attempted to determine in vitro conditions of experiment for obtaining relationship between different concentrations of heparin and values of APTT, and to investigate influence of factor VIII on correlation between concentrations of heparin and APTT. Measurement of the effect of heparin, added in vitro in normal coagulation control plasma (NCCP) showed that heparin in concentrations from 0.1 to 1.0 IU/mL prolonged APTT from 0.73 s to 99.26 s. Linearity of the relation of natural logarithm of APTT and concentration of added heparin in plasma for concentrations from 0.5 to 1.0 IU/mL (r = 0.995), and other characteristics of the validated method (RSD = 1.17%), made possible investigation of the influence of factor VIII addition in the solution. The addition of the Factor VIII concentrate, markedly influenced these APTT results. Increased factor VIII activity shortened the APTT, having more pronounced effect in the presence of the large amounts of heparin. Increased factor VIII was associated with downward shift in the concentration -- logAPTT response curve (y = 24644 x + 30.17 vs. y = 10.864 x + 27.256). This finding suggests the possibility for modeling of ex vivo establishment of correlation between plasma activity of FVIII and needed doses of heparin for appropriate management of heparin therapy.

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.

Plant material are used throughout developed and developing countries as home remedies, over the counter drug products and raw materials for the pharmaceutical industry and represent a substantial proportion of the global drug market. Medicinal plant materials normally carry a great number of bacteria and moulds, often originating in soil, while a large range of bacteria and fungi form the naturally occurring micro flora of herbs, aerobic spore-forming bacteria frequently predominate [1]. Eighty five herbal teas and sixteen herbal medicinal products obtained from different suppliers were examined for microbial contaminants. The maximum acceptable limits were determined according to European pharmacopoeia [2]. The microbiological examination was carried out in accordance with the Ph.Eur. The total aerobic plate counts for herbal teas were about 105 CFU/g, so the limits were met. The same applied to the moulds and yeasts whose aggregate values reached 104 CFU/g. While none of the herbal tea samples contained Salmonella spp., six samples exceeded the limit of 102 CFU/g for E. coli. The total aerobic plate counts for herbal medicinal products were about 102 CFU/g. References: [1] Beckmann, K. et al. (2003) Pharmeuropa 15: 291–298. [2] European Pharmacopoeia. (2005) Council of Europe. Strasbourg.

The screening of the antimicrobial activity of sage, rosemary, eucalyptus, melissa, lavender and thyme essential oils andactive compounds 1.8-cineole, citral, linalyl acetate and thymolwas conducted by a diffusion test against Gram-positiveand Gram-negative bacteria. The most active essential oils,eucalyptus and rosemary oils were tested for the minimal inhibitoryconcentration (MIC) and minimal bactericidal concentration(MBC). The activity was more pronounced againstGram-positive bacteria than against Gram-negative bacteriawith MIC ranging from 0.097 mg/ml-0.390 mg/ml, and MBCranging from 0.390 mg/ml-12.5 mg/ml.