Synthesis of unsymmetrical disulfanes bearing 1,2,4-triazine scaffold and their in vitro screening towards anti-breast cancer activity.

ABSTRACT: A new series of 1,2,4-triazine unsymmetrical disulfanes were prepared and evaluated as anticancer activity compounds against MCF-7 human breast cancer cells with some of them acting as low micromolar inhibitors. Evaluation of the cytotoxicity using an MTT assay, the inhibition of [3H]-thymidine incorporation into DNA demonstrated that these products exhibit cytotoxic effects on breast cancer cells in vitro. The most effective compounds with 59 and 60 µM compared to chlorambucil with 47 µM were disulfanes bearing methyl and methoxy substituent in an aromatic ring. Furthermore, all new 14 compounds were obtained with 22-74% yield via mild and efficient synthesis of the sulfur-sulfur bond formation from thiols and symmetrical disulfanes using 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ). The molecular structure of the newly obtained compounds was confirmed by X-ray analysis. The conformational preferences of disulfide system were characterized using theoretical calculations at DFT level and statistical distributions of C-S-S-C torsion angle values based on the Cambridge Structural Database (CSD). The DFT calculations and CSD searching show two preferential conformations for C-S-S-C torsion angle close to ± 90° and relatively large freedom of rotation on S-S bond in physiological conditions. The molecular docking studies were performed using the human estrogen receptor alpha (ERα) as molecular target to find possible binding orientation and intermolecular interactions of investigated disulfanes within the active site of ERα. The S…H-S and S…H-C hydrogen bonds between sulfur atoms of bisulfide bridge and S-H and C-H groups of Cys530 and Ala350 as protein residues play crucial role in interaction with estrogen receptor for the most anticancer active disulfane.

Structural mechanical properties of radiation-sterilized human Bone-Tendon-Bone grafts preserved by different methods.

To avoid the risk of infectious disease transmission from donor to recipient, allografts should be terminally sterilized. In the previous paper (Kaminski et al. in Cell Tissue Bank 10:215-219, 2009) we presented the effect of various methods of preservation (deep fresh freezing, glycerolization, lyophilization), followed by irradiation with different doses of electron beam (EB), on material (intrinsic) mechanical properties of human patellar tendons cut out as for anterior cruciate ligament reconstruction, obtained in failure tensile test. As structural mechanical properties are equally important to predict the behaviour of the graft as a whole functional unit, the purpose of the present paper was to show the results for failure load and elongation, obtained in the same experiment. Paired Bone-Tendon-Bone grafts (BTB) were prepared from cadaveric human patella tendons with both patellar and tibial attachments. They were preserved by deep freezing, glycerolization or lyophilization and subsequently EB-irradiated with the doses of 25, 35, 50 or 100 kGy (fresh-frozen grafts) or a single dose of 35 kGy (glycerolized and lyophilized grafts). Each experimental (irradiated) group was provided with control (non-irradiated), donor-matched group. The specimens from all groups were subjected to mechanical failure tensile test with the use of Instron system in order to measure their structural properties (failure load and elongation). All lyophilized grafts were rehydrated before mechanical testing. In our study we did not observe significant deterioration of structural mechanical properties of BTB grafts processed by fresh-freezing and then terminal sterilized with growing doses of EB up to 100 kGy. In contrast, BTB grafts processed by glycerolization or lyophilization and irradiated with 35 kGy showed significant decrease of failure load. Obtained results suggest that deep-frozen irradiated grafts retain their initial mechanical properties to an extent which does not exclude their clinical application. However, biomechanical investigations constitute only the first step to evaluate the potential clinical usefulness of such allografts and further extensive in vivo studies are needed.

Tissue banking training courses: Polish experience.

Personnel directly involved in the donation, procurement, testing, processing, preservation, storage and distribution of human tissues and cells should be appropriately qualified and provided with timely and relevant training according to EU directives. In the time of new tissue and cells regulations implementation such a training system existed in Poland only at a local level. The first training programme outlines for various groups of health professionals engaged in tissue banking practice was created in co-operation with the Institute for LifeLong Learning at University of Barcelona in 2006. This initial training courses were financially supported by EU Transition Facility Programme 2004. Then, starting from 2006, based on previous experience, system of advanced training courses was created. This training programme was financially supported by the National Programme for the Development of Transplantation Medicine 2006-2009-POLGRAFT financed by Polish Ministry of Health. During 2006 and 2007 first set of tissue banking initial training courses were provided according to TF 2004 project. Over 200 pathologists, forensic medicine specialists and other medical doctors responsible for donor screening and classification, medical directors of tissue establishments, technical staff; tissue graft users: orthopaedic surgeons, neurosurgeons, cardiosurgeons and ophthalmologists were trained. Between 2006 and 2009 there were organized 8 advanced tissue banking training courses according to POLGRAFT programme. There were organized both theoretical and practical courses on various aspects of tissue for over 350 persons. We present our experience in organisation of international and national tissue banking training courses.

Ethyl 2-(3-methyl-5-sulfanyl-idene-4,5-dihydro-1H-1,2,4-triazol-4-yl)acetate.

The title compound, C7H11N3O2S, exists in the 5-thioxo tautomeric form. The 1,2,4-triazoline ring is essentially planar, with a maximum deviation of 0.010 (2) Šfor the substituted N atom. The ethyl acetate substituent is almost planar, with a maximum deviation of 0.061 (4) Šfor the methyl-ene C atom of the eth-oxy group. The angle between the mean plane of this substituent and the mean plane of the 1,2,4-triazoline ring is 89.74 (8)°. In the crystal, mol-ecules are linked by a combination of N-H⋯S, C-H⋯N and C-H⋯O hydrogen bonds into chains parallel to [100].

Knowledge and opinions about tissue donation and transplantation among Polish students and physicians.

The idea of transplantation seems to be commonly identified by lay and professional people only with transplantation of vascularized organs like kidney or heart. The question arises whether there is any awareness of tissue transplantation among the public. A survey was therefore undertaken to assess awareness of and approaches to tissue donation and transplantation among selected social groups. A questionnaire on donation and transplantation issues was administered to respondents from the following groups: secondary school students, non-medical university students, medical university students, physicians. On the whole, 441 non-randomly sampled respondents were surveyed. The awareness of tissue transplantation is narrower than the awareness of organ transplantation. The support for tissue transplantation is weaker than for organ transplantation. This study shows that there is an acute need for education in the legal aspects of transplantation and that ways of motivating healthcare professionals to promote transplantation should be developed.