Physicochemical properties of lomefloxacin, levofloxacin, and moxifloxacin relevant to the biopharmaceutics classification system.

The aim of this investigation was to identify the impact of physicochemical properties of three fluoroquinolones (second, third, and fourth generation) on bioavailability in relation to the Biopharmaceutics Classification System (BCS) by in silico and in vitro methods. These properties were estimated by analyzing the electrostatic potential pattern and values of the free energy of solvation as well as the distribution coefficients and true partition coefficients of the studied compounds. This study was based on theoretical quantum-chemical methods and the in vitro shake-flask technique with two immiscible phases (n-octanol and phosphate buffer) as well as the experimental potentiometric method to estimate protonation macro- and micro-constants.

Chemical aspects of the primary ionization mechanisms in matrix-assisted laser desorption ionization.

It has been proposed that the primary ionization mechanism occurring in matrix-assisted laser desorption ionization (MALDI) experiments originates from the presence, in the solid-state matrix-analytes sample, of matrix dimers. These species are formed by the interaction of carboxylic groups present in the matrix molecules with the formation of strong hydrogen bonds. Theoretical calculations proved that the laser irradiation of these structures leads to one or two H-bridge cleavages, giving rise to an "open" dimer structure or to disproportionation with the formation of MH(+) and [M-H](-) species.

Prediction of bioavailability of selected bisphosphonates using in silico methods towards categorization into a biopharmaceutical classification system.

The physicochemical properties relevant to biological activity of selected bisphosphonates such as clodronate disodium salt, etidronate disodium salt, pamidronate disodium salt, alendronate sodium salt, ibandronate sodium salt, risedronate sodium salt and zoledronate disodium salt were determined using in silico methods. The main aim of our research was to investigate and propose molecular determinants thataffect bioavailability of above mentioned compounds. These determinants are: stabilization energy (deltaE), free energy of solvation (deltaG(solv)), electrostatic potential, dipole moment, as well as partition and distribution coefficients estimated by the log P and log D values.

Molecular properties impact on bioavailability of second generation triazoles antifungal agents.

The bioavailability of active compounds depends on their two main features: solubility and permeability. The experimental determination of these factors is rather cumbersome. The free enthalpies of salvation deltaG in water and chloroform, and the electrostatic potential surface around examined molecules were ab initio calculated by HF method for voriconazole, posaconazole and ravuconazole.

Endohedral complexes of fullerene C60 with small convalent molecules (H2O, NH3, H2, 2H2, 3H2, 4H2, O2, O3) in the context of potential drug transporter system.

The fullerene C60 has chemical properties which seem to predestinate it to be effective transporter of drugs in biological system. To prove this, the DFT/B3LYP (6-31G*) calculations were performed especially in order to determine the structures and energies of the inclusion complexes of C60 with small molecules. It was found that the small molecule is more compact when it is located in the centre of the C60 cage than as isolated molecule.

Model structure-activity relationship studies of potential tropane 5HT, 5HT, and D receptor ligands.

The two-stages studies of structure-activity relationship for model ligands of 5HT, 5HT, and D receptors were performed. On the first stage, the pharmacophores of two potential ligands of known in vitro binding to 5HT, 5HT, D receptors and model pharmacophore of strongly interacting D receptor ligands were found and their parameters were related to affinity data. The analyzed parameters were hydrophobic, hydrophilic, aromatic, donor and acceptor of proton centers.

Synthesis and biological evaluation of novel pyrrolidine-2,5-dione derivatives as potential antidepressant agents. Part 1.

A series of 3-(1H-indol-3-yl)pyrrolidine-2,5-dione derivatives was synthesized and their biological activity was evaluated. The chemical structures of the newly prepared compounds were confirmed by (1)H NMR, (13)C NMR and ESI-HRMS spectra data. All tested compounds proved to be potent 5-HT1A receptor and serotonin transporter protein (SERT) ligands.

On the Primary Ionization Mechanism(s) in Matrix-Assisted Laser Desorption Ionization.

A mechanism is proposed for the first step of ionization occurring in matrix-assisted laser desorption ionization, leading to protonated and deprotonated matrix (Ma) molecules ([Ma + H](+) and [Ma - H](-) ions). It is based on observation that in solid state, for carboxyl-containing MALDI matrices, the molecules form strong hydrogen bonds and their carboxylic groups can act as both donors and acceptors. This behavior leads to stable dimeric structures.

Metabolic stability of new anticonvulsants in body fluids and organ homogenates.

The stability as a function of time of compounds with established anticonvulsant activity: picolinic acid benzylamide (Pic-BZA), picolinic acid 2-fluorobenzylamide (Pic-2-F-BZA), picolinic acid 3-fluorobenzylamide (Pic-3-F-BZA), picolinic acid 4-fluorobenzylamide (Pic-4-F-BZA) and picolinic acid 2-methylbenzylamide (Pic-2-Me-BZA) in body fluids and homogenates of body organs were determined after incubation. It was found that they decompose relatively rapidly in liver and kidney and are stable against enzymes present in body fluids and some organs. These results are consistent with the bond strength expressed as total energy of amide bonds (calculated by quantum chemical methods) in the studied anticonvulsants.

Synthesis and biological investigation of potential atypical antipsychotics with a tropane core. Part 1.

The synthesis, structure, in vitro and in vivo pharmacological activities of 3β-acylamine derivatives of tropane (4a-n, 5a-g, 6a,b, 8a-c) are described. Among the investigated compounds, several displayed very high (in nM) affinity for the monoamine receptors 5-HT(1A), 5-HT(2A,) and D(2). The most interesting agent 6b revealed very high affinity for the 5-HT(2A) and D(2) receptors and high affinity for the 5-HT(1A) receptor.

Novel 4-aryl-pyrido[1,2-c]pyrimidines with dual SSRI and 5-HT(1A) activity. part 3.

A number of 4-aryl-5,6,7,8-tetrahydropyrido[1,2-c]pyrimidine with 3-(1,2,3,6-tetrahydro-pyridin-4-yl)-1H-indole or 2-methyl-3-(1,2,3,6-tetrahydro-pyridin-4-yl)-1H-indole residues were synthesized for further investigation of SAR in a group of pyrido[1,2-c]pyrimidine derivatives with dual 5-HT(1A)/SERT activity. Compounds 8a-8p were found to be potent ligands for both 5-HT(1A) and SERT with K(i) ranging from 28,3 to 642 nM and 42,4 nM-1,8 μM, respectively. Moreover compounds 8a, 8b, 8c, 8d, 8e and 8g were found to be selective agonists, while 8i as an antagonist of 5-HT(1A) presynaptic receptors in the inducible hypothermia test in mice.

The structure-bioavailability approach in antifungal agents.

The thermodynamic and electrostatic properties of antifungal triazole and imidazole derivatives: itraconazole, fluconazole, miconazole and ketoconazole molecules were calculated. The main aim of our investigations was to identify molecular determinants that have an effect on bioavailability of studied compounds. This is solvation energy estimated by the DeltaG values as well as electrostatic properties of the molecules.

Molecular properties of oxyconazole and tioconazole as the criteria for their bioavailability estimation.

The use of hydration and solvatation free enthalpies (DeltaG(h), DeltaG(s)) as parameters describing water solubility and permeability of drugs was proved to be suitable quantities. The free enthalpies of hydration and solvation by water and chlorobenzene molecules at the Hartree-Fock (6-31G*) level applying PCM model were calculated for oxyconazole and tioconazole. The oxyconazole and tioconazole differ in water and chlorobenzene solubility, what is reflected in calculated DeltaG values and electrostatic potential.

The usefulness of simple X-ray powder diffraction analysis for counterfeit control--the Viagra example.

Counterfeit and illegally manufactured drugs become a very important problem all over the world, hence, a search for new fast, easy, reliable and not expensive methods of drugs screening is essential. We describe the use of X-ray powder diffraction method for the fast screening of tablets for counterfeit medicines identification. The original Viagra tablets and some counterfeit and/or imitations of Viagra were used as example.