Generic substitution policy,an incentive approach

Generic substitution policy has been adopted in several countries in order to control health expenditures. Using a model based on incentives, this work aims to analyze the response of doctors and pharmaceutical companies to the implementation of this policy. It is shown that after the implementation of GSP, the effort of doctor’s convincing the patient to take generics increase or decrease depending on his level of concern for patient well-being; pharmaceutical companies decrease the amount of detailing and the market share of generics tends to increase.     

Factors affecting the reactivity and selectivity in the oxidation of sulfides with tetra-n-butylammonium peroxomonosulfate catalyzed by Mn(III) porphyrins: Significant nitrogen donor effects

The oxidation of aryl sulfides by tetra-n-butylammonium peroxomonosulfate (n-Bu₄NHSO₅) was carried out in the presence of six different manganese (III) tetraarylporphyrins [Mn(Por)s] as biomimetic catalysts and a number of nitrogen donors as co-catalysts. There is no noticeable difference between the reactivity of sulfides, in the presence of electron-rich Mn(por)s, whereas, for electron-deficient catalysts, conversion rates are different. Nevertheless, the over-oxidation of sulfoxide is more sensitive to both the nature of substituents attached to the sulfur atom in substrates as well as porphyrin complex structure. The degree of catalytic activity of Mn(Por)s for the formation of sulfone product increases as the following order: Mn(TPFPP)OAc < Mn[T(4-NO₂P)P]OAc < Mn(TDCPP)OAc < Mn(TPP)OAc < Mn(TMP)OAc < Mn[T(4-OMeP)P]OAc. Our results show that in the presence of electron-rich Mn(Por)s, the strong π-donor N-H imidazoles possess co-catalytic activity greater than that of strong σ-donor amines and weak π-donor pyridines. When electron-deficient Mn(Por)s were employed as catalyst, pyridines demonstrated a higher co-catalytic activity than that of N-H imidazoles. The pronounced effect of protic solvents on the rate and selectivity of oxidation reactions, particularly in the presence of electron-deficient Mn(Por)s has been observed. The outcome of our investigations accompanied by UV-Vis and Raman spectral data confirms the involvement of different active oxidant such as a high valent Mn-oxo species as well as a six-coordinate [(L)(Por)Mn-OHSO₄] complex.     

Structure-activity relationships for organometallic osmium arene phenylazopyridine complexes with potent anticancer activity

We report the synthesis and characterisation of 32 half sandwich phenylazopyridine Os(II) arene complexes [Os(η(6)-arene)(phenylazopyridine)X](+) in which X is chloride or iodide, the arene is p-cymene or biphenyl and the pyridine and phenyl rings contain a variety of substituents (F, Cl, Br, I, CF(3), OH or NO(2)). Ten X-ray crystal structures have been determined. Cytotoxicity towards A2780 human ovarian cancer cells ranges from high potency at nanomolar concentrations to inactivity. In general the introduction of an electron-withdrawing group (e.g. F, Cl, Br or I) at specific positions on the pyridine ring significantly increases cytotoxic activity and aqueous solubility. Changing the arene from p-cymene to biphenyl and the monodentate ligand X from chloride to iodide also increases the activity significantly. Activation by hydrolysis and DNA binding appears not to be the major mechanism of action since both the highly active complex [Os(η(6)-bip)(2-F-azpy)I]PF(6) (9) and the moderately active complex [Os(η(6)-bip)(3-Cl-azpy)I]PF(6) (23) are very stable and inert towards aquation. Studies of octanol-water partition coefficients (log P) and subcellular distributions of osmium in A2780 human ovarian cancer cells suggested that cell uptake and targeting to cellular organelles play important roles in determining activity. Although complex 9 induced the production of reactive oxygen species (ROS) in A2780 cells, the ROS level did not appear to play a role in the mechanism of anticancer activity. This class of organometallic osmium complexes has new and unusual features worthy of further exploration for the design of novel anticancer drugs.     

Studies on the constituents of the green alga <Emphasis Type="Italic">Ulva lactuca</Emphasis>

Phytochemical investigations on a marine green alga Ulva lactuca led to the isolation of two new compounds (E)-6-heptacosen-5-one (1) and (E)-6-octadecen-5-ol (2), along with four known compounds, (Z)-10-hexacosene (3), docosanoic acid (4), palmitic acid (5), and isofucosterol (6). Compounds 3 and 4 were isolated for the first time from this species. The structures of the compounds were deduced with the help of modern spectroscopic techniques.     

Synthesis, spectral, thermal and magnetic studies of Mn(II), Ni(II) and Cu(II) complexes with some benzopyran-4-one Schiff bases

The Schiff bases of N(2)O(2) dibasic ligands, H(2)La and H(2)Lb are prepared by the condensation of ethylenediamine (a) and trimethylenediamine (b) with 6-formyl-7-hydroxy-5-methoxy-2-methylbenzopyran-4-one. Also tetra basic ligands, H(4)La and H(4)Lb are prepared by the condensation of aliphatic amines (a) and (b) with 6-formyl-5,7-dihydroxy-2-methylbenzopyran-4-one. New complexes of H(4)La and H(4)Lb with metal ions Mn(II), Ni(II) and Cu(II) are synthesized, in addition Mn(II) complexes with ligands H(2)La and H(2)Lb are also synthesized. Elemental and thermal analyses, infrared, ultraviolet-visible as well as conductivity and magnetic susceptibility measurements are used to elucidate the structure of the newly prepared metal complexes. The structures of copper(II) complexes are also assigned based upon ESR spectra study. All the complexes separated with the stoichiometric ratio (1:1) (M:L) except Mn-H(4)La and Mn-H(4)Lb with (2:1) (M:L) molar ratio. In metal chelates of the type 1:1 (M:L), the Schiff bases behave as a dinegative N(2)O(2) tetradentate ligands. Moreover in 2:1 (M:L) complexes, the Schiff base molecules act as mono negative bidentate ligand and binuclear complex is then formed. The Schiff bases were assayed by the disc diffusion method for antibacterial activity against Staphylococcus aureus and Escherichia coli. The antifungal activity of the Schiff bases was also evaluated against the fungi Aspergillus flavus and Candida albicans.