Bożena Modzelewska-Banachiewicz

Synthesis and mycological activity of the compounds obtained in the reaction of N3-substituted amidrazones with sulphinyl-bis-2,4-dihydroxybenzenethioyl

2-Phenyl-5-(2,4-dihydroxybenzene)-1,3,4-thiadiazole (4), 2-(2-pyridyl)-2,4-dihydroxybenzene-1,3,4-thiadiazole (5), N(1)-2,4-dihydroxybenzenecarbothio-N(3)-phenyl-benzamidrazone (6) and N(1)-2,4-dihydroxybenzenecarbothio-N(3)-phenyl-2-picoline-amidrazone (7) were prepared and tested for their antimycotic activity. The chemical structures were confirmed by IR, 1H-NMR, EI-MS and elemental analysis. The minimal inhibitory concentration (MIC) values against dermatophytes, yeasts and moulds were determined for the estimation of potential activity in vitro. The strongest fungistatic activity for compound 5 in relation to dermatophytes was found with MIC 0.48-0.99 microg mL(-1).

Antiviral activity of the products of cyclization of dimethyl 2-[(1-arylamino-1-arylmethylidene)hydrazono]succinate

In this research, conditions of cyclization of dimethyl 2-[(1-arylamino-1-arylmethylidene)hydrazono]succinate 1-5 leading to the formation of 3,4-diaryl-5-carboxymethyl-1,2,4-triazole 6-10 and methyl 2-(5-oxo-3,4-diaryl-1,4,5,6-tetrahydro-1,2,4-triazine-6-ylidene)acetates 11-15 and the biological activity of some of them have been examined. Their chemical structures were confirmed by IR, 1H-NMR, EI-MS and elemental analysis. Substances 8 and 13 exhibited moderate virucidal activity and partially inhibited absorption of the viruses to the susceptible cells. The acute toxicity of compounds 6-10 was established. For compounds 8 and 13, the influence on the central nervous system of mice and rats in behavioral tests was examined.

Synthesis and anti-inflammatory activity of new 1,2,4-triazole derivatives

The series of new 1,2,4-triazole derivatives with methacrylic acid moiety were synthesized and characterized by NMR and IR spectroscopy as well as X-ray crystallography. The influence of newly synthesized compounds on the inflammation on the level of cytokine production and the proliferation of human peripheral blood mononuclear cells (PBMC) were experimentally evaluated. Obtained triazoles showed antiproliferative activity and diverse effects on cytokine production. Two compounds demonstrated potentially anti-inflammatory activity and comparable effects with ibuprofen.

Synthesis, crystal structure and biological activities of a novel amidrazone derivative and its copper(II) complex — A potential antitumor drug

A new linear amidrazone derivative, 6-acetyl-cyclohex-3-enecarboxylic acid [1-pyridin-2-yl-1-(pyridyn-2-yloamin)meth-(Z)-ylidene] hydrazide, H(2)L (2) and its Cu(II) complex, [Cu(2)L(2)]·4H(2)O (3) were synthesized and characterized by elemental analysis, IR and (1)H NMR spectroscopy and cyclic voltammetry. Compound 2 was synthesized in the equimolar reaction of N(3)-substituted amidrazone with cis-1,2,3,6-tetrahydrophthalic anhydride. The Cu complex of 2 was obtained in the reaction with copper(II) acetate. The molecular structures of 2 and 3 were determined by X-ray crystallography. The parent ligand exists in its amide-hydrazone form in the solid state. The central amidrazone moiety has a Z configuration with respect to the double C=N bond. Coordination to the metal center promotes Z/E isomerization of the hydrazone group of the ligand. Compound 3 is a dinuclear four-coordinated Cu(II) complex with the amidrazone ligand behaving as a tetradentate double deprotonated chelating one. Several biological activities of 2 and 3 were examined in vitro; they were: antimicrobial properties against selected bacterial and fungal strains, suppression of phytohemagglutinin A (PHA)-induced proliferation of human peripheral blood mononuclear cells (PBMC) and their effects on tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) production. The cytotoxic activity of Cu(II) complex was determined with respect to the four carcinoma cell lines (SW 984, CX-1, L-1210, A-431). The studied complex exhibited significant cytotoxic effects (particularly against CX-1 colon carcinoma), comparable to those reported for cisplatin. Both compounds have shown a relatively low antibacterial activity and were devoid of antifungal properties.

Reactions of N3‐Substituted Amidrazones with cis‐1,2‐Cyclohexanedicarboxylic Anhydride and Biological Activities of the Products

A series of novel compounds were synthesized in reactions of N3‐substituted amidrazones with cis‐1,2‐cyclohexanedicarboxylic anhydride: linear, isoindole, and triazole derivatives. All new structures were confirmed by H1 NMR and IR spectrometry as well as elemental analysis. Potential biological effects of new compounds were predicted with the Prediction of Activity Spectra for Substances (PASS) program. Antiviral, antibacterial, analgesic, and anti‐inflammatory activities were experimentally verified.

2-[4-Phenyl-5-(2-pyridyl)-4H-1,2,4-triazol-3-yl]nicotinic acid: a case of solvent-dependent polymorphism

The title compound, C(19)H(13)N(5)O(2), crystallizes in two monoclinic forms depending on the solvent used. From methanol or acetone, a yellow form [(Ia), m.p. 533 K] in the space group P2(1) is obtained, while with ethanol as the solvent, an orange form [(Ib), m.p. 541 K] in the space group Cc results. The conformers observed in the two polymorphs differ primarily in the relative orientation of pyridine/phenyl and triazole rings. Molecules of both polymorphs form chains through carboxyl O-H...N hydrogen bonding; however, in each crystal structure, a different group acts as acceptor, viz. a triazole and a pyridyl N atom for (Ia) and (Ib), respectively. This is the first case of polymorphism observed for crystals of a 3,4,5-trisubstituted 1,2,4-triazole derivative.

QSAR studies of a number of triazole antifungal alcohols.

The activity of fungicide agents containing a quinazolinone ring was described using the quantitative structure-activity relationship (QSAR) model by applying it to data taken from literature. The title compounds exhibit two important types of activity against certain fungal pathogens, i.e. activity against yeast and activity against filamentous fungi. A correlation between both antifungal activities (e.g. FA(yst) and FA(ff)) and physicochemical parameters such as the logarithm of the n-octanol/water partition coefficient (log P), the polarizability (P), the global minimum energy (TE), the energy difference between the frontier molecular orbital (DELH) and the molar refractivity (MR), was established using multiple linear regression. The molecular descriptors of the antifungal agents were obtained by quantum chemical calculations combined with molecular modeling calculations. Statistical analysis shows that the antifungal activity depends mainly on the calculated partition coefficients, log P, of the compounds. Bi-parametric models reveal that antifungal activity relates linearly to log P and P.

2-Allylaminothiazole and 2-allylaminodihydrothiazole derivatives: synthesis, characterization, and evaluation of bioactivity.

Some reactions of selected chlorooxoesters and haloesters with a 1-allylthiourea under various conditions have been performed. The reactions have been performed in methanol in alkaline and neutral environment. Condensation of 1-allylthiourea with chlorooxoesters has been further led via acetal as intermediate compound. As a result, the compounds containing thiazole and a 4,5-dihydrothiazole ring with a good yield have been obtained. The structures of the compounds were verified by 1H NMR, 13C NMR as well as X-ray diffraction analysis. Due to the potential biological activity of the synthesized compounds, the parameters of their bioavailability have been determined, and the probability of pharmacological action has been defined. All of the obtained compounds fulfilled the rule of five, which indicate their good absorption after oral intake. The probability of pharmacological action and potential targets calculated for the obtained compounds show that they can be potential drugs.Graphical abstract

Novel O-Benzyl Oxime Ethers of 1-(Thiophen-2-yl)ethan-1-one – Synthesis, Structure and Antimicrobial Activity

1 Department of Organic Chemistry, Collegium Medicum, Nicolaus Copernicus University, Jurasza 2, 85-094 Bydgoszcz, Poland, *E-mail: tpkos@wp.pl 2 Department of Genetic and Microbiology, Faculty of Biology and Biotechnology, Sklodowska-Curie University, Akademicka 19, 20-033 Lublin, Poland 3 Medicinal Chemistry Department, Collegium Medicum, Nicolaus Copernicus University, Jurasza 2, 85-094 Bydgoszcz, Poland 4 Department of Organic Chemistry, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznan, Poland

Lipophilicity Study of Thiazolo[3,2-a]pyrimidine Derivatives as Potential Bioactive Agents

Systems containing fused thiazole and pyrimidine rings play a significant role in organisms due to their biological activity. Lipophilicity, as important parameter to expect biological activity of the compounds, was evaluated for 27 potentially active thiazolo[3,2-a]pyrimidine derivatives using chromatographic methods: reversed phase thin layer chromatography (RP-TLC) and reversed phase high performance liquid chromatography (RP-HPLC) methods. Methanol was used as the organic modifier of the mobile phases. The corresponding relationship between compounds structure and lipophilicity parameters (RM0 and log kw) values were observed and featured. RM0 and log kw parameters were compared with computed log P values. For all of analyzed compounds, determined lipophilicitys parameters values are > 0 which means that there are hydrophobic substances, soluble in the lipid phase. Simultaneously, these values are < 5, i.e., are in accordance with Lipinskis rule in the range of lipophilicity. In the case of the possibility of their use as drugs, they will be active after oral application.