-
[show abstract]
[hide abstract]
ABSTRACT: Several N-substituted maleimides containing substituents of varying bulkiness and polarity were synthesised and tested for antimicrobial and cytostatic activity. Neutral maleimides displayed relatively strong antifungal effect minimum inhibitory concentrations (MICs in the 0.5-4 µg ml(-1) range); their antibacterial activity was structure dependent and all were highly cytostatic, with IC(50) values below 0.1 µg ml(-1). Low antimicrobial but high cytostatic activity was noted for basic maleimides containing tertiary aminoalkyl substituents. Chemical reactivity and lipophilicity influenced antibacterial activity of neutral maleimides but had little if any effect on their antifungal and cytostatic action. N-substituted maleimides affected biosynthesis of chitin and β(1,3)glucan, components of the fungal cell wall. The membrane enzyme, β(1,3)glucan synthase has been proposed as a putative primary target of N-ethylmaleimide and some of its analogues in Candida albicans cells.
Journal of Enzyme Inhibition and Medicinal Chemistry 05/2011; 27(1):117-24. · 1.62 Impact Factor
-
Angewandte Chemie International Edition 09/2003; 42(33):3903-6. · 13.45 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Several N-acyl and ester derivatives of 2-amino-2-deoxy-D-glucitol-6-phosphate (ADGP) have been synthesised and tested as inhibitors of fungal enzymes involved in early steps of chitin biosynthesis and for antifungal activity. All the tested derivatives were found to be much poorer inhibitors of the enzyme, D-glucosamine-6-phosphate (GlcN-6-P) synthase, than the parent compound but some of them exhibited much better antifungal activity. MIC values for the investigated compounds ranged between 10 mg mL(-1), found for ADGP and 0.3 mg mL(-1) for the most active derivative, namely ADGP dimethyl ester. Increased affinity of ADGP derivatives to the artificial immobilised cell membrane was correlated with their enhanced ability to be taken up by fungal cells by free diffusion. It was found that some of the examined derivatives behaved as 'pro-drugs' and after internalisation were converted into ADGP in the cell-free extract. This conversion was relatively rapid for ADGP esters but very slow for N-acyl derivatives. Results of our studies demonstrate a possibility of design and preparation of GlcN-6-P synthase inhibitors exhibiting antifungal activity.
Bioorganic & Medicinal Chemistry 05/2003; 11(8):1653-62. · 2.92 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The preparation and crystal structures of fourteen complexes of N,N'-bis(2-pyridyl)aryldiamines with dicarboxylic acids and two complexes with squaric acid are reported. The recognition between the carboxylic acids and the 2-aminopyridine units occurs through the formation of the cyclic R(2)2 (8) hydrogen bond motif, whereas squaric acid creates the analogous R(2)2 (9) motif. In the 1:1 complexes the cyclic motifs generate infinite hydrogen-bonded 1D networks with the alternating component molecules. These networks are further organised into densely packed layers assembled through weaker C-H...O interactions. Analysis of the intermolecular interactions in these complexes led us to the synthesis of N,N'-bis(2-pyridyl)-2,2'-oxybis(aminobenzene) (5) which acts as a tritopic receptor of the carboxylic group and forms exclusively 2:1 complexes with dicarboxylic acids.
Organic & Biomolecular Chemistry 05/2003; 1(8):1425-34. · 3.70 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The molecule of the title compound, C(8)H(11)NO(2), contains a strained bicyclic system with a significantly twisted imide chromophore. The five-membered ring fragment containing the imide function is strongly puckered and adopts a half-chair conformation. The six-membered ring has a slightly distorted chair conformation. The molecules are joined by strong N-H.O and weak C-H.O hydrogen bonds into infinite chains.
Acta Crystallographica Section C Crystal Structure Communications 12/2002; 58(Pt 11):o661-2. · 0.52 Impact Factor
-
04/2002;
-
04/2002;
-
[show abstract]
[hide abstract]
ABSTRACT: Several N-nitrosopiperidines with chirality solely due to a hindered rotation about the N−N bond were resolved to enantiomers by inclusion crystallization with optically active diols (TADDOLs). The absolute configuration of the guest nitrosamines was deduced from the X-ray crystal structures of the inclusion complexes. The enclathrated nitrosamines were liberated by a competitive complexation of the host diols with piperazine. The optical activity of the resolved nitrosamines is manifested by their CD spectra. A simple chirality rule was proposed for a rationalization of the observed Cotton effect sign corresponding to the n−π* electronic transition. The optically active nitrosamines are configurationally labile compounds and gradually racemize in solution but they are indefinitely stable in the solid state. The first-order kinetics of the racemization in solution allowed us to assign the N−N rotation barriers by simple polarimetric measurements.
The Journal of Organic Chemistry 12/2000; 66(2). · 4.45 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: N-nitrosamines, whose chirality is solely due to hindered rotation about the N−N bond, are enantioselectively enclathrated by the crystal host matrices of cholic or deoxycholic acid, as evidenced by X-ray crystallography (see structure in picture) and CD spectra.
Angewandte Chemie International Edition 02/1999; 38(3):392 - 395. · 13.45 Impact Factor
-
Tetrahedron Asymmetry 15(20):3257-3261. · 2.65 Impact Factor
-
Tetrahedron Asymmetry 8(8):1267-1273. · 2.65 Impact Factor
-
Tetrahedron Asymmetry 20(13):1472-1475. · 2.65 Impact Factor
-
Tetrahedron Asymmetry 16(22):3711-3717. · 2.65 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Two selenolactams with rigid 2-azabicyclo[2.2.1]heptane skeletons were prepared by reaction of the corresponding lactams with P4Se10. A comparison of their UV–vis and CD spectra with those of the carbonyl and thiocarbonyl analogues showed a similar character of the lowest-energy electronic transitions and the same signs of the corresponding Cotton effects. The MCD spectra of selenolactams revealed that their n–π* absorption band is dominated by the singlet–triplet component. A very weak CD corresponding to this component has an opposite sign to its much stronger singlet–singlet counterpart observed at the blue edge of the n–π* band.
Tetrahedron Asymmetry 10(21):4123-4128. · 2.65 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The CD spectra of several bicyclic lactams and thiolactams were measured in different solvents. The concentration dependence of the spectra observed in hydrocarbon solvents was attributed to shifts in the equilibrium between monomer and hydrogen-bonded dimer forms. The CD of some compounds is characterized by unusually strong Cotton effects resulting from non-planarity of the amide bonds due to internal strain of the bicyclic skeletons. The X-ray crystallographic structures of 2a,c, 3b,d and 4a,b showed different degrees of distortion of the amide or thioamide moieties from planarity, which causes inherent chirality of the chromophores and profoundly affects the Cotton effect sign and magnitude. This distortion also restricts application of the sector rules for prediction of the n–π* CD sign, since they can be used only for compounds with planar chromophores.
Tetrahedron Asymmetry 10(13):2591-2604. · 2.65 Impact Factor
-
Tetrahedron Asymmetry 18(12):1486-1494. · 2.65 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A general, facile method to synthesize the N gamma-alkyl and N gamma,N gamma-dialkyl derivatives of L-glutamine 1a-d from L-glutamic acid as a starting substrate is presented. The obtained compounds are shown to inhibit three different glutamine-utilizing enzymes, namely: glutaminase, gamma-glutamyl transpeptidase, and glucosamine-6-phosphate synthase, with inhibitory constants within the millimolar range.
Zeitschrift fur Naturforschung C 64(9-10):631-6. · 0.77 Impact Factor
