Irena Wolska

Comparative structural analysis of sparteine derivatives and their protonated salts

Abstract X-ray results on derivatives of sparteine and its salts with mineral acids have been reviewed. Attention has been paid to the factors which cause configurational and conformational transformations of the molecular skeleton.

Synthesis and pharmacological activity of O-aminoalkyl derivatives of 7-hydroxycoumarin

A series of novel O-aminoalkyl substituted 7-hydroxycoumarins were synthesized and evaluated for antibacterial and anticancer toxicity. Two different synthetic procedures, conventional and microwave assisted were used, and the structures of the compounds were confirmed by IR, 1H, 13C NMR and MAS spectroscopic data. The molecular and crystal structures of 8-acetyl-7-[2-(1-morpholino)ethoxy]4-methylchromen-2-one in solid state were analyzed by single crystal X-ray diffraction. The compound crystallizes in the monoclinic space group P2(1)/c. The main driving forces for the supramolecular structure are the C-H⋯O hydrogen bonds and the π⋯π intermolecular interactions. The most active compounds are those, where the O-aminoalkyl substituent has N,N-diethylamino part, and acetyl group is at C6 or at C8 atoms.

Synthesis of new hexahydro- and octahydropyrido[1,2-c]pyrimidine derivatives with an arylpiperazine moiety as ligands for 5-HT1A and 5-HT2A receptors.

Synthesis applied to prepare compounds 5-15 and 17-22 discussed in this paper has been presented in Scheme 1. Multi-stage preparation techniques were used to obtain 4-aryl-hexahydro 1-4 and (R,R) and (S,S) 4-aryl-octahydropyrido[1,2-c]pyrimidine-1,3-dione (16) derivatives, being the starting compounds for further modification. N-Alkylation of the imide group in compounds 1-4 and 16 followed, using 1,4-dibromobutane to yield monobromobutyl derivatives 5-8 and 17. Subsequent condensation of those compounds with appropriate 1-aryl or 1-heteroarylpiperazine led to the final hexahydro- 9-15 and octahydro- 18-22 pyrido[1,2-c]pyrimidine-1,3-dione derivatives. The final products were subjected to screening test to elucidate the affinity to 5-HT1A and 5-HT2A receptors.

Synthesis and biological investigation of potential atypical antipsychotics with a tropane core. Part 1.

The synthesis, structure, in vitro and in vivo pharmacological activities of 3β-acylamine derivatives of tropane (4a-n, 5a-g, 6a,b, 8a-c) are described. Among the investigated compounds, several displayed very high (in nM) affinity for the monoamine receptors 5-HT(1A), 5-HT(2A,) and D(2). The most interesting agent 6b revealed very high affinity for the 5-HT(2A) and D(2) receptors and high affinity for the 5-HT(1A) receptor. The in vivo head twitch model was used to demonstrate antagonism of the 5-HT(2A) receptor subtype by this compound. In another test, 6b caused hypothermia in mice, which was not attenuated by WAY 100635. In the climbing test, the compound did not significantly modify climbing behaviour following apomorphine administration. Moreover, 6b significantly reduced locomotor activity in mice. Molecular docking studies using a homology model of the 5-HT(1A) receptor revealed a significant role of the N-8 atom of the tropane core in stabilising the ligand-receptor complex due to strong hydrogen bonding with Asp116 located in the TMH 3 helix. Analogically, in a homology model of the 5-HT(2A) receptor, the N-8 atom formed a hydrogen bond with Gly369. In another homology model of the D(2) receptor, strong hydrogen bonding of the amide moiety in the 3β position of the tropane nucleus with Asp85 was observed. Compound 6b displayed a favourable Meltzer index (1.21) which is a feature of atypical antipsychotic agents.

Structure of 4-(4-methoxyphenyl)hexahydro-1H,3H-pyrido[1,2-c]pyrimidine in the solid state

Abstract The symmetry-independent part of the unit cell of 1 , C 15 H 16 N 2 O 3 , consists of two molecules of 1a , 1b . The variations in their geometry affect the location of the resonances in the 13 C CP MAS NMR spectrum in different ways. The calculations of shielding constants on the ab initio level of theory allowed for reliable assignments of signals.

Synthesis of Sulfur Containing Colchicine Derivatives and their Biological Evaluation as Cytotoxic Agents

Semi-synthetic C-10 alkyl thio analogues of the cytotoxic natural alkaloid colchicine have been found to exhibit cytotoxicity towards tumour cell lines at levels comparable to that of the natural product. An efficient synthesis of 10-alkyl thiocolchicines in mild conditions is proposed and the products are studied by H and C NMR, FT-IR, MS-EI methods and elementary analysis. The crystal structure of 10-ethylthiocolchicine is characterised using X-ray diffraction methods. Cytotoxic activity against selected cancer cell lines for all obtained 10-alkylthio analogues of colchicine is also reported.

Synthesis, spectroscopic studies and crystal structure of 5,5'-dimethoxy-3,3'-methanediyl-bis-indole as the inhibitor of cell proliferation of human tumors

Abstract 5,5’-Dimethoxy-3,3’-methanediyl-bis-indole (3) was synthesized in a reductive cyclisation process from (E)-5-methoxy-2-nitro-β -morpholinestyrene. The solid state structure was probed by single crystal X-ray diffraction and 13C CP/MAS NMR methods. The results of the X-ray analysis indicate insignificantly different structure of both methoxyindole fragments of the molecule, and this is the main reason for the appearance of the double resonances in the solid state NMR spectrum. Interesting N-H· · ·π interactions were observed which may have a functional role in biological features of 3. 5,5’- Dimethoxy-3,3’-methanediyl-bis-indole at conc. 1 · 10−4 M reduces the growth of MCF7 (breast), NCI-H460 (lung), and SF-268 (NCS) cells to 21, 0, and 48%, respectively.

Structural aspects of intermolecular interactions in the solid state of 1,4‐dibenzylpiperazines bearing nitrile or amidine groups

X-ray diffraction analyses for new pentamidine analogs are presented: 1,4-bis(4-cyanobenzyl)piperazine (1) crystallizes in the triclinic space group () and 1,4-bis(4-amidinobenzyl)piperazine tetrahydrochloride tetrahydrate (2) in the monoclinic space group (P21/n) revealing a complex system of hydrogen bonds for (2).

Model structure–activity relationship studies of potential tropane 5HT1A, 5HT2A, and D2 receptor ligands

The two-stages studies of structure–activity relationship for model ligands of 5HT1A, 5HT2A, and D2 receptors were performed. On the first stage, the pharmacophores of two potential ligands of known in vitro binding to 5HT1A, 5HT2A, D2 receptors and model pharmacophore of strongly interacting D2 receptor ligands were found and their parameters were related to affinity data. The analyzed parameters were hydrophobic, hydrophilic, aromatic, donor and acceptor of proton centers. The geometry of spatial distribution of these properties was also investigated in comparative analysis. The studied, model compounds were two 3β-acylamine derivatives of tropane. The second stage includes docking of studied compounds to D2 receptor model and the comparison of its quality with in vivo binding data. The obtained results are consistent with in vitro binding data and applied procedure accurate estimates the affinity of potential ligands to D2 receptors.

A Comparison of the Enamino Carbonyl Conjugation Efficiency for Hydrogen Bonding Formation in Pyridone and Dihydropyridone Systems

The crystal structures of two compounds containing enaminone heterodiene systems and forming intermolecular hydrogen bonds N-H·O are reported: 1) 3-ethoxycarbonyl-2-methyl-4-pyridone (hereafter ETPY) and 2) 3-ethoxycarbonyl-2-phenyl-6-methoxycarbonyl-5,6-di-hydro-4-pyridone (hereafter EPPY). The crystal packing is controlled by intermolecular hydro gen bonds N-H·O = C connecting the heteroconjugated enaminone groups in infinite chains. In ETPY crystals the intermolecular hydrogen bond involves the heterodienic pathway with the highest π-delocalization that is effective for a very short N·O distance of 2.701(9) Å (average from two molecules in the asymmetric unit). Probably due to the steric hindrance, the hydrogen bond in EPPY is formed following the heterodienic pathway that involves the ester C = O group, although π-delocalization along this pathway is less than that along the pyridone-part pathway resulting in a longer N·O distance of 2.886(3) Å