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The synthesis, in vitro evaluation and conformational study of penetratin and structurally related derivatives acting as antibacterial agents are reported. Among the compounds evaluated here, two methionine sulphoxide derivatives ( RQIKIWFQNRRM[ O] KWKK- NH2 and RQIKIFFQNRRM[ O] KFKK- NH2) exhibited the strongest antibacterial effect in this series. In order to better understand the antimicrobial activity obtained for these peptides, we performed an exhaustive conformational analysis using different approaches. Molecular dynamics simulations were performed using two different media (water and trifluoroethanol/water). The results of these theoretical calculations were corroborated using experimental CD measurements. The electronic study for these peptides was carried out using molecular electrostatic potentials obtained from RHF/6-31 G(d) calculations. In addition, the non-apeptide RQIRRWWQR- NH2 showed strong inhibitory action against the Gram-negative and Gram-positive bacteria tested in this study. [ABSTRACT FROM AUTHOR]

An ab initio and Density Functional Theory (DFT) study of the conformational properties of cyclododecane was carried out. The energetically preferred equilibrium structures, their relative stability, and some of the transition state (TS) structures involved in the conformational interconversion pathways were analyzed from RHF/6-31G(d), B3LYP/6-31G(d,p) and B3LYP/6311++G(d,p) calculations. Aug-cc-pVDZ//B3LYP/6311++G(d,p) single point calculations predict that the multistep conformational interconversion mechanism requires 11.07 kcal/mol, which is in agreement with the available experimental data. These results allow us to form a concise idea about the internal intricacies of the preferred forms of cyclododecane, describing the conformations as well as the conformational interconversion processes in the conformational potential energy hypersurface. Our results indicated that performing an exhaustive analysis of the potential energy curves connecting the most representative conformations is a valid alternate tool to determine the principal conformational interconversion paths for cyclododecane. This methodology represents a satisfactory first approximation for the conformational analysis of medium- and large-size flexible cyclic compounds. © 2011 Wiley Periodicals, Inc. Int J Quantum Chem, 2012 [ABSTRACT FROM AUTHOR]

A conformational and electronic study on N-acetyl-L-isoleucine-N-methylamide was carried out. All side-chain as well as backbone conformations were explored for this compound. Multidimensional conformational analysis predicts 81 structures in the case of N-acetyl-L-isoleucine-N-methylamide, 53 relaxed structures were determined at the DFT (B3LYP/6-31G(d)) level of theory. An exhaustive electronic study employing the atoms-in-molecules (AIM) method was carried out. In addition, the effects of three solvents (water, acetonitrile, and chloroform) were included in the calculations using the isodensity polarizable continuum model (IPCM) method. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2006 [ABSTRACT FROM AUTHOR]

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A conformational and electronic study on N-phenylalkyl-3,4-dichloromaleimides, a new series of antifungal compounds, was carried out. In this study ab initio [RHF/3-21G and RHF/6-31G(d)] and density functional theory (B3LYP/6-31G(d)) calculations were performed. The effect of solvent (water) was taken into account by performing calculations with the isodensity polarizable continuum model method. The electronic study of the compounds was carried out using molecular electrostatic potentials. The presence of two symmetrical aromatic systems reduces notably the conformational possibilities of these maleimides. The results permit the recognition of the minimal structural requirements for the production of the antifungal response; a 3,4-dichloroimido ring and a benzene ring appear to be indispensable. Also, theoretical calculations suggest that the optimum interatomic distance between these moieties is about 3.5–5.0 Å. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem, 2003 [ABSTRACT FROM AUTHOR]

Abstract: The design, synthesis, in vitro evaluation, and conformational study of nitrosopyrimidine derivatives acting as antifungal agents are reported. Different compounds structurally related with 4,6-bis(alkyl or arylamino)-5-nitrosopyrimidines were evaluated. Some of these nitrosopyrimidines have displayed a significant antifungal activity against human pathogenic strains. In this paper, we report a new group of nitrosopyrimidines acting as antifungal agents. Among them, compounds 2a, 2b and 15, the latter obtained from a molecular modeling study, exhibited antifungal activity against Candida albicans, Candida tropicalis and Cryptococcus neoformans. We have performed a conformational and electronic analysis on these compounds by using quantum mechanics calculations in conjunction with Molecular Electrostatic Potentials (MEP) obtained from B3LYP/6–31G(d) calculations. Our experimental and theoretical results have led us to identify a topographical template which may provide a guide for the design of new nitrosopyrimidines with antifungal effects. [Copyright &y& Elsevier]

Abstract: The synthesis, in vitro evaluation, and conformational study of penetratin analogues acting as antifungal agents are reported. Different peptides structurally related with penetratin were evaluated. Analogues of penetratin rich in Arg, Lys and Trp amino acids were tested. In addition, HFRWRQIKIWFQNRRM[O]KWKK-NH2, a synthetic 20 amino acid peptide was also evaluated. These penetratin analogues displayed antifungal activity against human pathogenic strains including Candida albicans and Cryptococcus neoformans. In contrast, Tat peptide, a well-known cell penetrating peptide, did not show a significant antifungal activity against fungus tested here. We also performed a conformational study by means experimental and theoretical approaches (CD spectroscopic measurements and MD simulations). The electronic structure analysis was carried out from Molecular Electrostatic Potentials (MEP) obtained by using RHF/6-31G ab initio calculations. Our experimental and theoretical results permitted us to identify a topographical template which may provide a guide for the design of new peptides with antifungal effects. [Copyright &y& Elsevier]

Abstract: The synthesis, in vitro evaluation, and conformational study of a new series of small-size peptides acting as antifungal agents are reported. In a first step of our study we performed a conformational analysis using Molecular Mechanics calculations. The electronic study was carried out using Molecular electrostatic potentials (MEPs) obtained from RHF/6-31G calculations. On the basis of the theoretical predictions three small-size peptides, RQWKKWWQWRR-NH2, RQIRRWWQWRR-NH2, and RQIRRWWQW-NH2 were synthesized and tested. These peptides displayed a significant antifungal activity against human pathogenic strains including Candida albicans and Cryptococcus neoformans. Our experimental and theoretical results allow the identification of a topographical template which can serve as a guide for the design of new compounds with antifungal properties for potential therapeutic applications against these pathogenic fungi. [Copyright &y& Elsevier]