Bożena Kuran

Use of RP‐HPTLC Systems for the Determination of Lipophilicity of 3,5‐Dioxo‐4‐azatricyclo[5.2.2.02,6]undecanes–5‐HT1A Antagonists

Abstract The lipophilicities of twelve 3,5‐dioxo‐4‐azatricyclo[5.2.2.02,6]undecanes, potential serotonergic 5‐HT1A receptors antagonists, was determined by means of the reversed‐phase RP‐18W and RP‐18 thin‐layer chromatography. The use of the linear (Soczewinski‐Wachtmeister) and square (Schoenmaker) equation for R MW calculation was evaluated. Due to the rather poor correlation between linear and square R MW values, despite very good correlation coefficients for independent measurements for each solvent system, the results of the RP‐18 measurements and use of the linear equation for the R MW calculation were found to be the most reliable. Their reliability was also confirmed by the best values of F and s. The standardization (for six standards of known lipophilicity – log P) allowed calculation of the experimental lipophilicities (log P EXP ) for compounds investigated.

Synthesis and antimicrobial activity of derivatives of 1H-benzo[de]isoquinoline-1,3(2H)-dione

Abstract Five aminoalkyl 1H-benzo[de]isoquinoline-1,3(2H)-diones were synthesized and evaluated for antimicrobial activity. Microorganisms used in this study included aerobic and facultative anaerobic bacteria Staphylococcus aureus, Escherichia coli and Stenotrophomonas maltophilia, and obligatory anaerobes Bacteroides fragilis, Bacteroides thetaiotaomicron and Propionibacterium acnes. Moreover, Candida albicans yeast was used. The minimum inhibitory concentration (MIC) was determined for the test compounds. Among the tested derivatives, two compounds 1 and 2 have shown the most potent antibacterial as well as antifungal activities.

Synthesis of Conformationally Constrained Aryl- or Heteroarylpiperazinyl Derivatives of Selected Imides as 5-HT1A Receptor Ligands

The preparation of a number of cyclic imide 5-HT(1A) receptor ligand derivatives has been described. Their structures were conformationally constrained by introducing rigid linkers containing unsaturated bonds or aromatic benzene rings. These compounds are expected to possess anxiolytic and antidepressant activity.

Synthesis and biological activity of novel series of heterocyclic compounds containing succinimide moiety

Abstract In the search for biological agents, a series of new N-substituted ethyl 11-ethyl-7-methyl-3,5,10-trioxo-4-azatricyclo[5.2.2.02,6]undecane-8-carboxylates 3, 9-methyl-3,5,8-trioxo-4-azatricyclo[5.2.1.02,6]dec-1-yl acetates 6 and 1,3-dioxo-4,5,6,7-tetraphenyl-2,3,3a,4,5,7a-hexahydro-1H-isoindole-4-carboxylic acids 9 were prepared. All compounds were characterized by 1H NMR, ESI-MS, and elemental analyses. Moreover, for intermediate products 2, 5, and 8, X-ray structural analyses were conducted. Compounds 3a–e, 6a, 6b, 9a–e were tested for their cytotoxic properties in K562 and HeLa cells.

New, Substituted Derivatives of Dicarboximides and their Cytotoxic Properties.

A large group of aminoalkyl and aminoalkanol derivatives of selected dicarboximides were synthesized and characterized by 1HNMR, 13CNMR and ESI MS spectra analysis. The thirty nine new compounds were tested for their cytotoxic properties in human chronic (K562), acute leukemia (HL-60), and cervical cancer cells (HeLa) as well as in normal endothelial cells (HUVEC). The most promising compounds are 4-[2-(dimethylamino)ethyl]-, (diethylamino) ethyl]-, 4-[2-(piperidin-1-yl)ethyl]-, 4-[3-(dimethylamino)propyl]- and 4-[2-hydroxy-3-(propan- 2-ylamino)propyl]- derivatives of 1,7-diethyl-8,9-diphenyl-4-azatricyclo[5.2.1.0(2,6)]dec-8-ene-3,5,10-trione exhibiting high and selective cytotoxicity towards K562 and HL-60 cells (IC50 in the range of 1-10 µM) while being non-toxic towards HUVEC and HeLa cells (IC50> 100 μM). Moreover, the preliminary studies have showed that 4-[2-(piperidin-1-yl)ethyl]- 1,7-diethyl-8,9-diphenyl-4-azatricyclo [5.2.1.0(2,6)]dec-8-ene-3,5,10-trione induces programmed cell death (apoptosis) in leukemia cells.

Synthesis and preliminary studies of biological activity of amino derivatives of 4-azatricyclo- [5.2.1.02,6]dec-8-ene-3,5-dione with silicon in the structure

Abstract A series of 38 new derivatives of cyclic imides containing silicon in the structure was synthesized and characterized by 1H NMR, ESI-MS, and elemental analysis. Selected compounds (1l,m, 1g, 1o,p, 2l,m, and 2o,p) were tested for their cytotoxic properties in human chronic myelogenous leukemia (K562), human cervical cancer (HeLa), and normal endothelial cells (HUVEC). Seven compounds showed significant cytotoxicity. In addition, two compounds (1l and 2l) were tested toward affinity for 5-HT1A, 5-HT6, and 5-HT7 serotonin receptors, and all aryl/heteroarylopiperazino derivatives were tested for antimicrobial activity. The compounds tested toward affinity for selected serotonin receptors showed high and moderate affinity for 5-HT1A and 5-HT7, while the antimicrobial activity of tested compounds was not significant.

Synthesis and biological activity of 6-substituted 5-acetyl-4,7-dimethoxybenzofuran derivatives

Abstract In the search for new antimicrobial and anticancer agents, a series of (aryl/heteroaryl-piperazino-alkyl)-substituted derivatives of benzo[b]furans were prepared. All compounds were characterized by 1H NMR, 13C NMR, ESI-MS spectra and elemental analyses. Most of the investigated compounds had no antimicrobial activity (MIC > 512 mg/L) except for 2l, 2m and 2o, which showed activity against Candida albicans. None of the tested compounds showed significant anticancer activity in K562 and HeLa cells.