Synthesis and antifungal activity of new hybrids pyrimido[4,5-d]pyridazinone-N-acylhydrazones.

Paracoccidioidomycosis is an endemic mycosis in Latin America for which there is a high mortality rate and limited treatment options. There are no specific drugs to treat the systemic disease. Thus, there is a need for further studies focused on the development of specific drugs.

Novel 4-methoxynaphthalene--acylhydrazones as potential for paracoccidioidomycosis and tuberculosis co-infection.

 17 new 4-methoxynaphthalene--acylhydrazones were synthesized in order to evaluate their biological action against important pathogens.   susceptibility assays of compounds were performed against and . Compounds , and were the most potent against , two with minimum inhibitory concentrations of ≤1 μg ml and exhibited pharmacological synergy with amphotericin B.

Eugenol and derivatives activity against Mycobacterium tuberculosis, nontuberculous mycobacteria and other bacteria.

Aim: To evaluate (i) the in vitro activity of eugenol (EUG) and three derivatives against Mycobacterium tuberculosis (Mtb), nontuberculous mycobacteria (NTM) and other bacteria, (ii) the EUG and antituberculosis drugs combinatory effect and (iii) the EUG and its derivatives cytotoxicity.

Materials & Methods: Minimum inhibitory concentration of the compounds were determined by resazurin microtiter or broth microdilution assay and the drug interaction between EUG and antituberculosis drugs by resazurin drug combination microtiter. The cytotoxicity was carried out in macrophages, HeLa and VERO cells.

New 4-methoxy-naphthalene derivatives as promisor antifungal agents for paracoccidioidomycosis treatment.

Aim: Novel 4-methoxy-naphthalene derivatives were synthesized based on hits structures in order to evaluate the antifungal activity against Paracoccidioides spp.

Methods: Antifungal activity of compounds was evaluated against P. brasiliensis and most promising compounds 2 and 3 were tested against eight clinically important fungal species.

NMR spectroscopy and theoretical calculations in the conformational analysis of 1-methylpyrrolidin-2-one 3-halo-derivatives.

This study reports the results of ab initio and density functional theory (DFT) electronic structure calculations as well as (3)J(HH) experimental and calculated coupling constant data obtained in the investigation of the conformational equilibrium of 3-halo-derivatives of 1-methylpyrrolidin-2-one. The five-membered ring assumes an envelope conformation owing to the plane of formation of the O═C-N-R bond, with C4 forming the "envelope lid". When the conformation changes, the "lid" alternates between positions above and below the amide plane.

The conformational analysis of 2-halocyclooctanones.

The establishment of the most stable structures of eight membered rings is a challenging task to the field of conformational analysis. In this work, a series of 2-halocyclooctanones were synthesized (including fluorine, chlorine, bromine and iodine derivatives) and submitted to conformational studies using a combination of theoretical calculation and infrared spectroscopy. For each compound, four conformations were identified as the most important ones.

Infrared and theoretical calculations in 2-halocycloheptanones conformational analysis.

2-Halocycloheptanones (Halo=F, Cl, Br and I) were synthesized and their conformational analysis was performed through infrared spectroscopy data. The corresponding conformers geometries and energies were obtained by theoretical calculations at B3LYP/aug-cc-pVDZ level of theory in the isolated state and in solution. It was observed, by both approaches, that the conformational preferences were very sensitive to the solvent polarity, since its increase led to an increase in the population of the more polar conformer.

Conformational analysis of cis-2-halocyclohexanols; solvent effects by NMR and theoretical calculations.

Conformational problems often involve very small energy differences, even low as 0.5 kcal mol(-1). This accuracy can be achieved by theoretical methods in the gas phase with the appropriate accounting of electron correlation.

Effect of sulfur oxidation on the transmission mechanism of 4J(HH) NMR coupling constants in 1,3-dithiane.

Long-range 4J(HH) couplings in 1,3-dithiane derivatives are rationalized in terms of the effects of hyperconjugative interactions involving the S=O group. Theoretical and experimental studies of 4J(HH) couplings were carried out in 1,3-dithiane-1-oxide (2), cis-1,3-dithiane-1,3-dioxide (3), 1,3-dithiane-1,1,3-trioxide (4), and 1,3-dithiane-1,1,3,3-tetraoxide (5) compounds. Hyperconjugative interactions were studied with the natural bond orbital, NBO, method.

The prediction of (1)H chemical shifts in amines: a semiempirical and ab initio investigation.

Twenty one conformationally fixed amines and their N,N-dimethyl derivatives were obtained commercially or synthesized. These included cis and trans 4-t-butyl cyclohexylamine, 2-exo and 2-endo norbornylamine, 2-adamantylamine, 4-phenylpiperidine, 1-napthylamine and tetrahydro-1-napthylamine. The (1)H NMR spectra of these amines were measured in CDCl(3) solution, assigned and the (1)H chemical shifts given.