No abstract

A series of thirteen new megazol derivatives, designed exploring the molecular hybridization approach between megazol (3) and heterocombretastatins (2), was synthesized. These new compounds were tested for in vitro antiparasitic activity upon axenic amastigotes of Leishmania donovani. Biological results led us to identify a new potent megazol derivative (4g), which presents an IC(50) = 0.081microg/mL, more active tham the reference drug miltefosine (IC(50) = 0.131microg/mL).

Various complexes of DHA with transition-metal cations are known for their antifungal properties. Here, four novel Zn and Cd complexes were prepared via the substitution of water by pyridine andg-picoline using Zn(DHA)2(H2O)2 (2) and Cd(DHA)2(H2O)2 (3) as starting materials. The products were characterized by IR, UV, elemental analysis, TGA and NMR techniques, including correlation times and intermolecular distance measurements using the NULL pulse sequence. The experimental data were compared to the molecular modeling results using DFT and the semiempirical method PM3, confirming that the pentacoordinated Zn complexes have bipyramidal geometry while the Cd complexes have the expected octahedral geometry. These results show that substitution of Zn by Cd leads to an important modification of the coordination structure, especially when strong ligands are involved.

The USP HPLC method for quantitative determination of nevirapine in suspension formulations was evaluated to determine its ability to resolve nevirapine and its major related impurities. The method was modified and an overall satisfactory resolution for all components was obtained by changing the column temperature to 25°C, the organic modifier to methanol, the mobile phase ratio to 50 %, adding 1 % HCl into the diluents, decreasing the flow rate from 1.5 to 1.2 mL mL -1 and using an isocratic mode. The related organic impurities were synthesized in high yield. The method is shown to be linear with coefficient of determination around 0.999 to nevirapine (Nvp) and related impurities were resolved using a mobile phase of potassium phosphate/phosphoric acid buffer (pH 2.5; 10 mM): methanol (50:50, v/v) on a BDS Hypersil C18 5 lm, 250 9 4.6 mm column. Accuracy ranged from 100.2 to 101.1 % and 100.0 to 100.5 % for nevirapine and related impurities, respectively. Repeatability from all experiments achieved RSD values \0.95 %. The detection and quantification limits were determined in the level of ng mL -1 . This method easily separated all known impurities synthesized and can be employed for routine analysis of suspension containing nevirapine in the presence of its impurities.