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A series of 78 synthetic 7-chloro-(4-thioalkylquinoline) derivatives were investigated for cytotoxic activity against eight human cancer as well as 4 non-tumor cell lines. The results showed, with some exceptions, that sulfanyl 5 - 40 and sulfinyl 41 - 62 derivatives exhibited lower cytotoxicity for cancer cell lines than those of well-described sulfonyl N-oxide derivatives 63 - 82 . As for compound 81 , the most pronounced selectivity (compared against BJ and MRC-5 cells) was observed for human cancer cells from HCT116 (human colorectal cancer with wild-type p53) and HCT116p53-/- (human colorectal cancer with deleted p53), as well as leukemia cell lines (CCRF-CEM, CEM-DNR, K562, and K562-TAX), lung (A549), and osteosarcoma cells (U2OS). A good selectivity was also detected for compounds 73 and 74 for leukemic and colorectal (with and without p53 deletion) cancer cells (compared to MRC-5). At higher concentrations (5 × IC 50 ) against the CCRF-CEM cancer cell line, we observe the accumulation of the cells in the G0/G1 cell phase, inhibition of DNA and RNA synthesis, and induction of apoptosis. In addition, X-ray data for compound 15 is being reported. These results provide useful scientific data for the development of 4-thioalkylquinoline derivatives as a new class of anticancer candidates.

The coexistence of leishmaniasis, Chagas disease, and neoplasia in endemic areas has been extensively documented. The use of common drugs in the treatment of these pathologies invites us to search for new molecules with these characteristics. In this research, we report 16 synthetic chalcone derivatives that were investigated for leishmanicidal and trypanocidal activities as well as for antiproliferative potential on eight human cancers and two nontumor cell lines. The final compounds 8−23 were obtained using the classical base-catalyzed Claisen−Schmidt condensation. The most potent compounds as parasiticidal were found to be 22 and 23, while compounds 18 and 22 showed the best antiproliferative activity and therapeutic index against CCRF-CEM, K562, A549, and U2OS cancer cell lines and non-toxic VERO, BMDM, MRC-5, and BJ cells. In the case of K562 and the corresponding drug-resistant K562-TAX cell lines, the antiproliferative activity has shown a more significant difference for compound 19 having 10.3 times higher activity against the K562-TAX than K562 cell line. Flow cytometry analysis using K562 and A549 cell lines cultured with compounds 18 and 22 confirmed the induction of apoptosis in treated cells after 24 h. Based on the structural analysis, these chalcones represent new compounds potentially useful for Leishmania, Trypanosoma cruzi, and some cancer treatments.

Cardiac glycosides (CGs) represent a group of sundry compounds of natural origin. Most CGs are potent inhibitors of Na + /K + -ATPase, and some are routinely utilized in the treatment of various cardiac conditions. Biological activities of other lesser known CGs have not been fully explored yet. Interestingly, the anticancer potential of some CGs was revealed and thereby, some of these compounds are now being evaluated for drug repositioning. However, high systemic toxicity and low cancer cell selectivity of the clinically used CGs have severely limited their utilization in cancer treatment so far. Therefore, in this study, we have focused on two poorly described CGs: hyrcanoside and deglucohyrcanoside. We elaborated on their isolation, structural identification, and cytotoxicity evaluation in a panel of cancerous and noncancerous cell lines, and on their potential to induce cell cycle arrest in the G2/M phase. The activity of hyrcanoside and deglucohyrcanoside was compared to three other CGs: ouabain, digitoxin, and cymarin. Furthermore, by in silico modeling, interaction of these CGs with Na + /K + -ATPase was also studied. Hopefully, these compounds could serve not only as a research tool for Na + /K + -ATPase inhibition, but also as novel cancer therapeutics.

Objective: Literature review of endometrial receptivity in embryo implantation and its diagnostic possibilities., Design: Literature review., Setting: Department of Obstetrics and Gynecology, University Hospital, Faculty of Medicine, Palacky University, Olomouc; Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc., Results: Endometrial tissue is very dynamic, undergoing cyclic proliferation, differentiation and cell transportation, especially of immune system cells under the influence of circulating estradiol and progesterone. Endometrial remodelling during embryo implantation is controlled by decidual cells senescence and effectivity of their immunologic destruction. Endometrial receptivity can be assessed by transcriptomic profiling of endometrial biopsy using ERA system or proteomic analysis of either endometrial secretome or cervical mucus by gel electrophoresis (DIGE) or mass spectrometry (MS)., Conclusion: With respect to recent discoveries in endometrial physiology and molecular biology, clinical application of proteomic approaches in research of potential biomarkers of endometrial receptivity could be of interest.

Background: Bronchial asthma is a chronic inflammatory disease of the respiratory tract where variety of cells plays a role, particularly mast cells, eosinophils (Eo), and T lymphocytes. At present, there is no clear-cut clinical or laboratory parameter to monitor the activity of this disease. Our study was designed to examine and compare serum eosinophilic cationic protein (S-ECP) levels, plasma ET-1 (P-ET) levels and percentage of eosinophils with CD44 (EoCD44) in paediatric asthmatic patients., Methods and Results: In our study, a group of 97 atopic children with persisting mild asthma, had a detailed analysis of their personal history. In addition, S-ECP, P-ET, EoCD44, eosinophil blood count (Eo) and serum levels of IgE(S-IgE) in peripheral blood were determined. Subsequently, children were treated with montelukast (singular), a leukotriene receptor antagonist for a period of three weeks (montelukast tablets in a dose of 5 mg once a day). A second S-ECP, P-ET, EoCD44 were determined in the interval of 3 months from the first collection. In 97 asthmatic children a correlation between P-ET and EoCD44 (p=0.002; r= -0.5) were found., Conclusions: Our follow-up study surprisingly confirmed a correlation between P-ET and EoCD44. The lower percentage of EoCD44 in peripheral blood in asthmatic children is due to Eo inflammation activity and attests the massive Eo invasion into the airways. The determination of combination - S-ECP, P-ET, EoCD44 - provides an indirect evidence of the multiple features of Eo inflammation.

The luminol-dependent chemiluminiscence of monocytes and granulocytes and the effect of autologous thrombocytes upon the chemiluminiscence activity were investigated in multiple sclerosis patients, patients with other neurological diseases and healthy controls. The spontaneous monocyte chemiluminiscence was found to be significantly higher in multiple sclerosis patients than in healthy controls. However, no differences were found between multiple sclerosis patients and the group of other neurological diseases. Addition of autologous thrombocytes did not substantially alter both the spontaneous and the zymozan-stimulated monocyte chemiluminiscence. No significant differences in granulocyte spontaneous and stimulated chemiluminiscence were found between the multiple sclerosis patients and both control groups. In all multiple sclerosis patients the addition of autologous thrombocytes markedly depressed the spontaneous and stimulated granulocyte chemiluminiscence and a similar effect was observed in most of the patients with other neurological diseases. In healthy controls, the effect of autologous thrombocytes was rather more heterogenous and both a thrombocyte-dependent increase and a decrease of the granulocyte chemiluminiscence were found. The results suggest that platelets are able to suppress the granulocyte oxidative burst and that this scavenger mechanism can be activated in multiple sclerosis and some other neurological diseases.