Izolda Segal

Synthesis, physicochemical characterization, cytotoxicity, antimicrobial, anti-inflammatory and psychotropic activity of new N-[1,3-(benzo)thiazol-2-yl]-ω-[3,4-dihydroisoquinolin-2(1H)-yl]alkanamides.

A series of new N-[(benzo)thiazol-2-yl]-2/3-[3,4-dihydroisoquinolin-2(1H)-yl]ethan/propanamide derivatives was synthesized and characterized by (1)H, (13)C NMR and IR spectroscopy and mass-spectrometry. A single crystal X-ray study of N-(1,3-benzothiazol-2-yl)-2-[3,4-dihydroisoquinolin-2(1H)-yl]ethanamide is reported to determine its conformational feature. The investigated compounds were found to be active in psychotropic in vivo, anti-inflammatory in vivo and cytotoxicity in vitro screening. They possess marked sedative action, reveal high anti-inflammatory activity, have selective cytotoxic effects and NO-induction ability concerning tumour cell lines. Some of the compounds synthesized demonstrate antimicrobial action. An attempt was made to correlate the biological results with their structural characteristics and physicochemical parameters. Some specific combinations of types of activities for the synthesized compounds have been revealed.

Synthesis and Neurotropic Activity of Novel Quinoline Derivatives

Hydroxyalkyl and carboxyalkyl derivatives of silatetrahydroisoquinoline, tetrahydroisoquinoline and tetrahydroquinoline have been synthesized. Their neurotropic activity has been investigated.

Organosilicon-containing thiazole derivatives as potential lipoxygenase inhibitors and anti-inflammatory agents.

A number of trimethylsiloxyalkyl and trialkylsilylalkyl thiazole derivatives have been evaluated for their anti-inflammatory activity, lipoxygenase inhibiting properties, and cytotoxicity. The investigated compounds have been found to protect in vivo against carrageenin-induced edema, especially 3-(4-trimethylsiloxypiperidin-1-yl)-N-(thiazol-2-yl)-propionamide (21) and 2-amino-3-(γ-trimethylsilylpropyl)thiazolium iodide (22), which exhibited good anti-inflammatory activity: 57.2% CPE inhibition in dose of 0.2 mmol/kg for compound 21 and 55.0% in dose of 0.01 mmol/kg for compound 22. All the compounds tested inhibited soybean lipoxygenase activity. 2-(4-Trimethylsilyloxypiperidin-1-yl)-N-[4-(p-methoxyphenyl)-thiazol-2-yl]-acetamide (19) was the most potent displaying inhibition against lipoxygenase (ID50 = 0.01 mmol). It also possessed moderate cytotoxic effect (LC50 = 13 μ g/mL, 3 × 10−8 mmol/mL) concerning MG-22A cell lines.

Synthesis and biological evaluation of lipid-like 5-(2-hydroxyethyl)-4-methyl-1,3-thiazole derivatives as potential anticancer and antimicrobial agents

A series of new lipid-like thiazole derivatives have been synthesized in good yields by O-alkylation of 5-(2-hydroxyethyl)-4-methyl-1,3-thiazole, a thiamine metabolite, under phase transfer catalysis conditions followed by N-alkylation with the aim to obtain potential anticancer and antimicrobial agents. The synthesized cationic amphiphiles and their ether precursors were subjected to in vitro cytotoxic evaluation against monolayer human fibrosarcoma HT-1080 and mouse hepatoma MG-22A tumour cell lines and normal mouse NIH 3T3 fibroblasts and were screened for antimicrobial activity concerning gram-positive and gram-negative bacterial and fungal strains. The synthesized compounds possessed strong antimicrobial activity, significant selective cytotoxicity and high NO-induction ability. In vivo investigation of 3,4-dimethyl-5-(2-undecyloxyethyl)-1,3-thiazol-3-ium iodide confirmed anticancer action, reliably inhibiting mouse sarcoma S-180 tumour growth.

Synthesis and 1H, 13C, 14N, 15N, 29Si NMR study of trimethylsilylquinolines and their methiodides

Abstract 2-, 3-, 4-, 5-, 6-, 7- and 8-trimethylsilylquinolines and their methiodides as well as some 2-silyl-alkylquinolines were obtained by lithium synthesis in order to elucidate intramolecular donor-acceptor interactions between nitrogen and silicon atoms. 1 H, 13 C, 14 N, 15 N and 29 Si NMR spectra of the compounds were studied and quantum-chemical calculation of charges on individual atoms in the unsubstituted quinoline and in trimethylsilylquinoline molecule was carried out. The two-centered component of the total system energy for various bonds was calculated. The findings suggest donor-acceptor interaction between nitrogen and silicon atoms in 2-trimethylsilylquinoline that reduces electron density at nitrogen atoms. An apparently weaker interactions is observed in 8-trimethylsilylquinoline.

Silyl Modification of Biologically Active Compounds. 14. Organosilicon Lipid-like Derivatives of Hydroxyethyl Tetrahydro(iso)quinoline and Thiazole with Antitumour, Antibacterial and Antifungal Properties

Purpose A series of novel lipid-like O- and N-(3-trimethylsilyl)propyl derivatives of N-(2-hydroxyethyl)-1,2,3,4-tetrahydroquinoline, -tetrahydroisoquinoline and 5-(2-hydroxyethyl)-4-methyl-1,3-thiazole have been obtained in order to facilitate penetration of biologically active small molecules through the plasma membrane and/or to enable their immobilization on the surface of magnetic nanocarriers for drug delivery application.MethodsThe synthesized compounds have been characterized by 1H, 13C and 29Si NMR spectroscopy and mass-spectrometry, evaluated for cytotoxicity on monolayer human fibrosarcoma HT-1080 and mouse hepatoma MG-22A tumour cell lines and normal mouse fibroblasts NIH 3T3, and screened for antimicrobial activity against gram-positive and gram-negative bacterial and fungal strains. Their inhibitory action towards topoisomerase II has also been investigated.ResultsThe obtained organosilicon compounds possessed high selective cytotoxicity (LC 50<1 µg ml -1) towards tumour cells and NO-induction ability, exhibited strong antimicrobial activity with MIC and MBC/MFC values of 0.5–32 µg ml-1 for the most active ones.ConclusionsThe lipid-like organosilicon derivatives of hydroxyethyl tetrahydro(iso)quinoline and thiazole exhibit an interesting combination of inhibitory activities towards tumours and bacterial cells and fungi. The pharmacological effect ranged from moderate to significant and increased upon quaternization. Compounds possessing high cytotoxicity and strong antibacterial and antifungal activity can be further developed as potential monotherapeutic agents for treatment infections in cancer patients instead of combination anticancer and anti-infective pharmacotherapy.

Iron oxide/oleic acid magnetic nanoparticles possessing biologically active choline derivatives: Synthesis, morphology, antitumor, and antimicrobial properties

Abstract In recent years, synthetic magnetic nanoparticles have made a major contribution to biomedicine. Interest in iron oxide magnetic nanoparticles conditioned by the fact that they are nontoxic, and possess the unique opportunity to deliver medicines to certain organs by external magnetic field. We have developed a synthetic procedure, which is based on binding of the first biologically active substance with the magnetic core, and subsequent immobilization of another biologically active substance (ligand) on the modified surface of nanoparticles thus creating plasma membrane-like structures. Using the proposed methodology, we have obtained new nontoxic magnetic nanoparticles, functionalized with pre-synthesized aliphatic and heterocyclic choline analogues, and determined their composition, structure, and size by different physicochemical methods. Interaction of the obtained nanoparticles with tumor cells and normal fibroblasts, as well as, bacterial cells and fungi has been evaluated. The resulting magnetic fluids revealed superparamagnetic properties and affected tumor and microbial cells.