Biomedical subjects
Publications and source records attributed to M Zinić.
The molecule of benzene-1,4-dicarboxamidine or benzdiamidine, C(8)H(10)N(4), reveals C(i) symmetry. Hydrogen bonds utilize the amino groups as double donors, whereas the imino groups act as double acceptors. The network formed is similar to that observed in the crystal packing of terephthalamide.
Bis(LeuOH) (1a), bis-(ValOH) (2a) and bis(PhgOH) (5a) (Phg denotes (R)-phenylglycine) oxalyl amides are efficient low molecular weight organic gelators of various organic solvents and their mixtures as well as water, water/DMSO, and water/DMF mixtures. The organisational motifs in aqueous gels are dominated primarily by lipophilic interactions while those in organic solvents are formed by intermolecular hydrogen bonding. Most of the gels are thermoreversible and stable for many months. However, 2a forms unstable gels with organic solvents which upon ageing transform into variety of crystalline shapes. For some 1a/alcohol gels, a linear correlation between alcohol dielectric constants (epsilon) and gel melting temperatures (Tg) was found. The 1H NMR and FTIR spectroscopic investigations of selected gels reveal the existence of temperature dependent network assembly/dissolution equilibrium. In the 1H NMR spectra of gels only the molecules dissolved in entrapped solvent could be observed. By using an internal standard, the concentration of dissolved gelator molecules could be determined. In FTIR spectra, the bands corresponding to network assembled and dissolved gelator molecules are simultaneously present. This enabled determination of the Kgel values by using both methods. From the plots of InKgel versus 1/T, the deltaHgel values of selected gels have been determined (-deltaHgel in 10-36 kJ mol(-1) range) and found to be strongly solvent dependent. The deltaHgel values determined by 1H NMR and FTIR spectroscopy are in excellent agreement. Crystal structures of 2a and rac-5a show the presence of organisational motifs and intermolecular interactions in agreement with those in gel fibres elucidated by spectroscopic methods.
In the title compound, C20H22N4O4*C2H6OS, two distinct hydrogen-bond systems connect oxalamide groups in one pattern and primary amide groups in the other to form a two-dimensional network perpendicular to the c axis. These hydrophilic layers are joined to the three-dimensional structure through C--H...pi interactions. The hydrogen-bonded waved layers shape holes which are occupied by disordered dimethyl sulfoxide solvent molecules.
The title compound, 2,2'-(oxalyldiimino)bis(3-methylbutanoic acid), C12H20N2O6, possesses a centre of symmetry. In the crystal, molecules are connected by hydrogen bonds between oxamide and carboxyl groups, similar to the pattern of the monoclinic forms of HO-Gly-CO-CO-Gly-OH and HO-Aib-CO-CO-Aib-OH (Gly is glycine and Aib is 2-aminoisobutyric acid). The characteristic torsion angles in the title compound are close to those in peptide alpha-helices.
DNA intercalating agents interfere with DNA's role as a template in replication and transcription by inserting an intercalator molecule between adjacent base pairs. We synthesized three potential novel intercalators, 4,9-diazapyrenium hydrogensulfate derivatives: 5, 10-diphenyl-4,9-dimethyl-4,9-diazapyrenium hydrogensulfate (FDAP), 4, 9-dimethyl-4,9-diazapyrenium hydrogensulfate (GDAP) and 2,4,7, 9-tetramethyl-4,9-diazapyrenium hydrogensulfate (MDAP) and tested their biological effects in vitro on four human tumor cell lines (SKBr3: breast carcinoma, HeLa: cervical carcinoma, CaCo2: colon carcinoma and SW620: poorly differentiated cells from lymph node metastasis of colon carcinoma). Cytotoxic effects on cell growth and viability were determined using tetrazolium dye (MTT) assay. DNA synthesis and proliferation of treated cells were studied by the [(3)H]-thymidine incorporation test. DNA fragmentation was analyzed by agarose gel electrophoresis. The growth inhibitory effect was cell-specific and dose-dependent. The most pronounced antiproliferative effect was observed on SKBr3 cells for FDAP (10(-5) M) 91.8%, for MDAP (10(-5) M) 85.3% and on SW620 cells for GDAP (10(-5) M) 65.3%. The DNA ladder fragmentation of treated HeLa and SKBr3 cells, as a hallmark of apoptosis, was observed. Based on specific DNA fragmentation, morphological changes (reduced cell volume, round cell shape, condensed chromatin) and growth inhibition of treated human tumor cells we conclude that tested substances induced apoptotic cell death.
We investigated the antiproliferative effects of two planar 4,9-diazapyrenium hydrogenasulphates against human malignant MiaPaCa 2 (pancreatic carcinoma), Hep 2 (laryngeal carcinoma) and human normal fibroblasts (WI 38) cell lines. The tested compounds were very potent in inhibiting the growth of the treated cell lines. Treatment with molar concentrations of the substances (10(-4)-10(-7) M) caused growth inhibition by more than 50%. The morphological changes of treated cells were also observed. Cells became smaller, with condensed chromatin and fragmented nuclei, the characteristics of dying cells. The identification of DNA-fragmentation and the appearance of chromatin aggregation leads us to assume the tested substances induced apoptosis of the investigated tumor cell lines.