Newly synthesized palladium(II) complexes with dialkyl esters of (S,S)-propylenediamine-N,N'-di-(2,2'-di-(4-hydroxy-benzil))acetic acid: in vitro investigation of biological activities and HSA/DNA binding.

The four new ligands, dialkyl esters of (S,S)-propylenediamine-N,N'-di-(2,2'-di-(4-hydroxy-benzil))acetic acid (R2-S,S-pddtyr·2HCl) (R = ethyl (L1), propyl (L2), butyl (L3), and pentyl (L4)) and corresponding palladium(II) complexes have been synthesized and characterized by microanalysis, infrared, 1H NMR and 13C NMR spectroscopy. In vitro cytotoxicity was evaluated using the MTT assay on four tumor cell lines, including mouse mammary (4T1) and colon (CT26), and human mammary (MDA-MD-468) and colon (HCT116), as well as non-tumor mouse mesenchymal stem cells. Using fluorescence spectroscopy were investigated the interactions of new palladium(II) complexes [PdCl2(R2-S,S-pddtyr)]; (R = ethyl (C1), propyl (C2), butyl (C3), and pentyl (C4)) with calf thymus human serum albumin (HSA) and DNA (CT-DNA). The high values of the binding constants, Kb, and the Stern-Volmer quenching constant, KSV, show the good binding of all complexes for HSA and CT-DNA. The mentioned ligands and complexes were also tested on in vitro antimicrobial activity against 11 microorganisms. Testing was performed by the microdilution method, where the minimum inhibitory concentration (MMC) and the minimum microbicidal concentration (MMC) were determined.

Synthesis, characterization, HSA binding, molecular docking, cytotoxicity study, and antimicrobial activity of new palladium(II) complexes with propylenediamine derivatives of phenylalanine.

The four new ligands, propylenediamine derivatives of phenylalanine (R2-S,S-pddbaˑ2HCl; L1-L4) and their palladium(II) complexes (C1-C4) were synthesized and characterized by elemental analysis, infrared, 1H and 13C NMR spectroscopy. The interactions of new palladium(II) complexes with human serum albumin (HSA) were studied by fluorescence spectroscopy. All investigated compounds can be transported to target cells by binding to HSA, but complex C4 interacts most strongly. Molecular docking simulations were applied to comprehend the binding of the complex to the molecular target of HSA. Obtained results are in good correlations with experimental data regarding binding affinity by HSA. In vitro cytotoxicity activities were investigated on four tumor cell lines (mouse mammary (4 T1) and colon (CT26), human mammary (MDA-MD-468) and colon (HCT116)) and mouse mesenchymal stem cells as non-tumor control cells. Cytotoxic capacity was determined by MTT test and according to obtained results ligand L4 stands out as the most active and selective compound and as a good candidate for future in vivo testing. Further examination of the ligand L4 and corresponding complex C4 led to the conclusion that both induced cell death mainly by apoptosis. Ligand L4 facilitated cycle arrest in G0/G1 phase and decreased proliferative capacity of tumor cells. In vitro antimicrobial activity for ligands and corresponding Pd(II) complexes was investigated against eleven microorganisms (eight strains of pathogenic bacteria and three yeast species) using microdilution method. The minimum inhibitory concentration and minimum microbicidal concentration were determined.

Synthesis, characterization, DNA interactions and biological activity of new palladium(II) complexes with some derivatives of 2-aminothiazoles.

Newly palladium(II) complexes (C1, C2) with derivatives of 2-aminothiazoles (L1 = 2-amino-6-methylbenzothiazole, L2 = 2-amino-6-chlorobenzothiazole), general formula [PdL2Cl2] were synthesized and characterized by elemental microanalyses, IR, NMR spectroscopy and X-ray spectroscopy in case of [Pd(L2)2Cl2]. The kinetic of the substitution reactions of complexes and the nucleophiles, such as guanosine-5'-monophosphate (5'-GMP), tripeptide glutathione (GSH) and amino acid L-methionine (L-Met), were studied by stopped-flow technique. The complex C2 was always more reactive, while the order of the reactivity of the nucleophiles, due to the associative mode of the reaction, was L-Met > GSH > 5'-GMP. In order to determine the type of interactions between palladium(II) complexes and calf thymus DNA (CT-DNA), we used electronic absorption spectroscopy, viscosity measurements, and fluorescence spectroscopic studies, while interactions with bovine serum albumin (BSA) were determined only with fluorescence spectroscopic studies. The observed results confirmed that both complexes bound to DNA by groove binding. The significantly strong interaction with BSA, especially for complex C2, was also observed. In vitro cytotoxic activity was evaluated against four tumor cell lines, 4 T1, CT26, MDA-MB-468, HCT116 and mesenchymal stem cells (mMSC). C1 complex showed higher cytotoxic activity against CT26 cell line. Flow cytometry analysis showed that C1 stimulated apoptosis of tumor cells via inhibition of expression of antiapoptotic Bcl-2 molecule and decelerated proliferation by decreasing Cyclin-D and increasing expression of P21. In vitro antimicrobial activity for ligands and corresponding palladium(II) complexes was investigated by microdilution method and minimum inhibitory concentration (MIC) and minimum microbicidal concentration (MMC) were determined. Tested compounds exhibited selective and moderate activity.

Does a probability of breech presentation of more than 50% exist among diseases and medical conditions?

The aim was to study the effect of twin gestations in a uterus with 2 bodies on the probability of breech presentation at delivery. The hypothesis was that the probability of breech presentation was not higher than 50%. A review was undertaken of MEDLINE (1966-2004) and of the article reference list for statistical analysis of presentation at delivery among twins in a normal uterus, singleton gestations in a uterus with 2 bodies, and case studies of twins in a uterus with 2 bodies. There are 10 studies of twin gestations in a normal uterus (Twin A 3036 cases, breech presentation 22.36%; Twin B 2758 cases, breech presentation 36.87%), 2 studies of singleton gestations in a uterus with 2 bodies (297 cases, breech presentation 42.09%), and 57 case report studies of twin gestations in a uterus with 2 bodies (Twin A 56 cases, breech presentation 14.29%; Twin B 54 cases, breech presentation 18.52%). The odds ratio and chi-square test for differences in probabilities show a significantly lower incidence of breech presentation for twins in a uterus with 2 bodies compared with twins in a normal uterus (Twin A, odds ratio = 0.58; chi(2) = 2.08, p > .05, Twin B, odds ratio = 0.39, chi(2) = 7.67, p < .05), and singleton gestations in a uterus with 2 bodies (Twin A, odds ratio = 0.23, chi(2) = 15.51, p < .05; Twin B, odds ratio = 0.31, chi(2) = 10.72, p < .05). Twin gestations in a uterus with 2 bodies decrease the probability of breech presentation.

Probability of breech presentation and its significance.

Existing data related to the probability of breech presentation suggest that the breech presentation is a consequence of mere filling of the intrauterine space, with the same probability of breech and cephalic presentation. As a consequence, group of cephalic presenting fetuses is heterogeneous. Some fetuses randomly assume the cephalic presentation while others assume cephalic presentation 'intentionally' for a reason. Before comparing breech and cephalic presenting fetuses/newborns, bias should be eliminated by subtracting from the cephalic-presenting group the number of fetuses/newborns that is identical with the number of breech-presenting fetuses/newborns with identical characteristics. The subtracted group should be added to the breech-presenting group before comparison with the remaining cephalic-presenting fetuses/newborns. The comparison should be corrected for the gestational age and according to data that are not influenced by delivery. Data suggest that the physiological process that accounts for 92% of cephalic-presenting human fetuses at delivery should be sought from the 25th gestational week onwards.