Izabela Dybała

Crystal structure, antitumour and antimetastatic activities of disubstituted fused 1,2,4-triazinones

Molecular structure of 3,8-disubstituted 7,8-dihydroimidazo[2,1-c][1,2,4]triazin-4(6H)-ones (8-14) was confirmed by X-ray crystallography of 14. All the compounds were evaluated for their antitumour and antimetastatic activities in vitro. Furthermore, their cytotoxicities towards human normal cell line-HSF cells were established, allowing us to point out some structure-activity relationships. Among them, imidazotriazinone 12, revealing remarkable dose-dependent viability decreases in human myeloma RPMI 8226 cells, was found to be completely non-toxic towards normal HSF cells. In addition, heterobicycles 8-12 were proved to exhibit significant antimetastatic potentials in the motility assay.

Synthesis and pharmacological activity of new carbonyl derivatives of 1-aryl-2-iminoimidazolidine: Part 1. Synthesis and pharmacological activity of chain derivatives of 1-aryl-2-iminoimidazolidine containing urea moiety

The synthesis and physicochemical properties of new carbonyl derivatives of 1-aryl-2-iminoimidazolidine are presented. Isomeric 1-(1-arylimidazolidine-2-ylidene)-3-arylureas (series A) and 1-aryl-2-imine-3-arylaminocarbonylimidazolidines (series B) were obtained after the condensation reaction of 1-aryl-2-iminoimidazolidines and arylisocyanates. 1-Aryl-2-iminoimidazolidines were synthesised in a two-step reaction from the respective anilines. The molecular structure of 1-(1-phenylimidazolidine-2-ylidene)-3-(4-chlorophenyl)urea (A2) has been determined by X-ray crystallography. The representatives of both investigated series were evaluated in behavioural animal tests. They exhibited significant, especially analgesic, activity on the animal central nervous system (CNS). They displayed substantial effect on the serotonine and catecholamine neurotransmission as well, at very low toxicity (LD(50) over 2000 mg kg(-1) i.p.). In the binding affinity tests they exhibited moderate affinity (on the micromolar level) toward opioid (mu) and serotonine (5HT(2)) receptors. The derivatives of series A had moderate affinity toward benzodiazepine (BZD) receptor as well. Distinctive differences observed in their activity spectra can be connected with the presence of particular structural features such as relative orientation of the two aromatic rings and the carbonyl moiety.

4-Azatricyclo[5.2.2.02,6]undecane-3,5,8-triones as Potential Pharmacological Agents

A series of twenty six arylpiperazine and aminoalkanol derivatives of 4-aza-tricyclo[5.2.2.02,6]undecane-3,5,8-trione have been prepared. The synthesized compounds were evaluated for their cytotoxicity and anti-HIV-1 activity in MT-4 cells.

Synthesis and Evaluation of in Vitro Biological Activity of 4-Substituted Arylpiperazine Derivatives of 1,7,8,9-Tetrachloro- 10,10-dimethoxy-4-azatricyclo(5.2.1.0 2,6 )dec-8-ene-3,5-dione

A series of twenty arylpiperazine derivatives of 1,7,8,9-tetrachloro-10,10-dimethoxy-4-azatricyclo[5.2.1.02,6]dec-8-ene-3,5-dione have been prepared. These derivatives were tested in vitro with the aim of identifying novel lead compounds active against emergent and re-emergent human and cattle infectious diseases (AIDS, hepatitis B and C, tuberculosis, bovine viral diarrhea). In particular, these compounds were evaluated in vitro against representatives of different virus classes, such as a HIV-1 (Retrovirus), a HBV (Hepadnavirus) and the single-stranded RNA+ viruses Yellow fever virus (YFV) and Bovine viral diarrhea virus (BVDV), both belonging to the Flaviridae. Compounds 2c, 2g and 3d showed a modest activity against CVB-2. The molecular structures of the starting imide 1 and one of propyl-piperazine derivatives, 3b, have been determined by an X-ray crystallography study.

Biological evaluation of novel 1,4-dithiine derivatives as potential antimicrobial agents

The preparation of twelve aminoalkanol derivatives of 2,3-dihydro-5H-[1,4]dithiino[2,3-c]pyrrole-5,7(6H)-dione was described. Newly obtained compounds, as well as their propyl and butyl analogues, were evaluated in vitro against selected viruses. Selected derivatives were tested for their antibacterial and antifungal activity. Compounds 3h, 3j, 4b and 5a–d showed moderate to significant protections against CVB-2, HSV-1 and YFV viruses. The molecular structures of 4a, 5c and 5g were determined by an X-ray analysis.

NMR QSAR Model for the Analysis of 4-(5-Arylamino-1,3,4-thiadiazol-2-yl)benzene-1,3-diols

We have developed a NMR data quantitative structure‐activity relationship NMR‐QSAR model based on 1H‐ and 13C‐NMR experimental spectral data of 4‐(5‐arylamino‐1,3,4‐thiadiazol‐2‐yl)benzene‐1,3‐diols. Compounds show in‐vitro antiproliferative activity against some human cancer cell lines. Two‐parameter equations obtained by the multiple linear regression procedure showed that chemical shifts of the protons of hydroxyl groups and carbon atoms of the 1,3,4‐thiadiazole ring are the decisive descriptors of inhibition interactions of the compounds. The models gave leave‐one‐out (LOO) cross‐validation ranges from 78% to 93%. The obtained NMR‐QSAR equations provide a rapid, reliable, and simple way for predicting the antiproliferative activity of N‐substituted 4‐(5‐amino‐1,3,4‐thiadiazol‐2‐yl)benzene‐1,3‐diols.

CCDC 758464: Experimental Crystal Structure Determination

Related Article: A.Bielenica, J.Kossakowski, M.Struga, I.Dybala, P.La Colla, E.Tamburini, R.Loddo|2011|Med.Chem.Res.|20|1411|doi:10.1007/s00044-010-9513-0