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.

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.

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.