Chemotherapy with anthracycline antibiotics is a common method of treating tumors of various etiologies. To create more highly effective cytostatics based on daunorubicin, we used the method of reductive amination using polyalkoxybenzaldehydes. The obtained derivatives of the anthracycline structure have much greater cytotoxicity compared to daunorubicin due to increased affinity for DNA, the ability to disrupt the cell cycle, and their inhibition of the glycolysis process, which is confirmed by data from extensive biological studies and the results of molecular modeling.
Cell culturing methods in its classical 2D approach have limitations associated with altered cell morphology, gene expression patterns, migration, cell cycle and proliferation. Moreover, high throughput drug screening is mainly performed on 2D cell cultures which are physiologically far from proper cell functions resulting in inadequate hit-compounds which subsequently fail. A shift to 3D culturing protocols could solve issues with altered cell biochemistry and signaling which would lead to a proper recapitulation of physiological conditions in test systems. Here, we examined porous ultra-high molecular weight polyethylene (UHMWPE) as an inexpensive and robust material with varying pore sizes for cell culturing. We tested and developed culturing protocols for immortalized human neuroblastoma and primary mice hippocampal cells which resulted in high rate of cell penetration within one week of cultivation. UHMWPE was additionally functionalized with gelatin, poly-L-lysine, BSA and chitosan, resulting in increased cell penetrations of the material. We have also successfully traced GFP-tagged cells which were grown on a UHMWPE sample after one week from implantation into mice brain. Our findings highlight the importance of UHMWPE use as a 3D matrix and show new possibilities arising from the use of cheap and chemically homogeneous material for studying various types of cell-surface interactions further improving cell adhesion, viability and biocompatibility.
We present the results of a histological study into the cardiotoxicity of conjugates of daunorubicin with dehydrocostus lactone and epoxyisoalantolactone in mature male mice of the C57BL/6 line. The effect of conjugates on the morphology of cardiomyocytes and the structure of the left ventricular myocardium in mice was studied.