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.
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.Graphical abstract
Electronic supplementary materialThe online version of this article (10.1007/s00706-018-2206-y) contains supplementary material, which is available to authorized users.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.