Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare acquired polyneuropathy that especially among youngest children should be differentiated with hereditary neuropathies. Even though upon diagnosis treatment options are similar in children and adults, diagnostic challenges are faced in the pediatric population. We conducted a retrospective analysis of clinical symptoms, nerve conduction study results, modes of treatment, and final outcome in 37 children aged 3.
View Article and Find Full Text PDFChemical modification of known, effective drugs is one method to improve chemotherapy. Thus, the object of this study was to generate melphalan derivatives with improved cytotoxic activity in human cancer cells (RPMI8226, HL60 and THP1). Several melphalan derivatives were synthesised, modified in their two important functional groups.
View Article and Find Full Text PDFAccurate profiling of the lipophilicity of amphoteric compounds might be complex and laborious. In the present work the lipophilicity of 12 anthracycline antibiotics-four parent drugs: doxorubicin, daunorubicin, epidoxorubicin, and epidaunorubicin and eight novel formamidyne derivatives with attached morpholine, hexamethylenoimine or piperidine rings-was determined based on novel approach using MEEKC. In the second stage, lipophilicity was correlated with anthracycline toxicity towards two cell lines.
View Article and Find Full Text PDFThe present study investigated the effect of cladribine (CLA) and six of its derivatives containing a formamidine group at position 6 (CLA-FDM, CLA-FPAZ, CLA-FPIR, CLA-FPIP, CLA-FHEX, and CLA-FMOR) on acute promyelocytic, lymphoblastic, and acute monocytic leukemia cells. The role of ATR kinase in deoxycytidine kinase (dCK) activation in response to DNA damage was assessed. The presence of DNA lesions was assessed by measurement phosphorylation of H2AX and by using the alkaline comet assay with proteinase K post-treatment following assessment of the cell cycle.
View Article and Find Full Text PDFChemical modification of known, effective drugs are one method to improve the chemotherapy of tumors. We reported ability of oxazoline analogs of doxorubicin (O-DOX) and daunorubicin (O-DAU) to induce apoptosis and autophagy in ovarian and liver cancer cells. Reactive oxygen and nitrogen species (ROS and RNS, respectively), together with intracellular calcium-mediated downstream signaling, are essential for the anticancer effect of these new anthracycline analogs.
View Article and Find Full Text PDFBackground/aim: Oxazolinodoxorubicin (O-DOX) and oxazolinodaunorubicin (O-DAU) are derivatives of anthracyclines (DOX and DAU) with a modified daunosamine moiety. We aimed to clarify their mechanisms of action by investigating intracellular accumulation and effects on the cell cycle, phosphatidylserine externalization, and proteasome 20S activity.
Materials And Methods: Experimental model consisted of SKOV-3, A549 and HepG2 cells.
Background/aim: Epidoxorubicin is an anthracycline agent. The present study was undertaken to compare the antileukemic potential of epidoxorubicin and its two formamidine analogs containing either a morpholine moiety (EPIFmor) or a hexamethyleneimine moiety (EPIFhex) in the amidine group.
Materials And Methods: The experiments were performed in vitro on MOLT-4 cells using spectrophotometry, Coulter electrical impedance, flow cytometry, and light microscopy methods.
J Chromatogr B Analyt Technol Biomed Life Sci
August 2017
The thermodynamic acid dissociation constants (pK and pK) of 16 anthracycline antibiotics, including doxorubicin (DOX) and daunorubicin (DAU), their epimers, epidoxorubicin (EDOX) and epidaunorubicin (EDAU), as well as novel anthracycline derivatives containing piperidine (FPIP), morpholine (FMOR) and hexamethylenoimine (FHEX) rings in the formamidine group of the daunosamine moiety were determined by analysis of the dependence between measured electrophoretic mobility and the pH of the buffer using the capillary zone electrophoresis method. The results obtained confirmed the ampholytic character of anthracyclines with at least two ionization states. The determined values were in the range of 8.
View Article and Find Full Text PDFOxazolinodoxorubicin (O-DOX) and oxazolinodaunorubicin (O-DAU) are novel anthracycline derivatives with a modified daunosamine moiety. In the present study, we evaluated the cytotoxicities, genotoxicities and abilities of O-DOX and O-DAU to induce apoptosis in cancer cell lines (SKOV-3; A549; HepG2), and compared the results with their parent drugs. We assessed antiproliferative activity by MTT assay.
View Article and Find Full Text PDFObjective: Dopa-responsive dystonia (DRD) is a rare form of hereditary movement disorder with onset in childhood, characterized by gait difficulties due to postural dystonia with marked improvement after low doses of levodopa. Mutations in the GCH1 gene are the most common cause of DRD, however, in some cases when the disease is associated with parkinsonism mutations in the PARK2 gene may be identified. The aim of this study was to analyze and compare genotype-phenotype correlation.
View Article and Find Full Text PDFSpectrochim Acta A Mol Biomol Spectrosc
December 2016
A broad spectroscopic characterization, using ultraviolet-visible (UV-vis) and Fourier transform infrared absorption as well as Raman scattering, of two commonly used anthracyclines antibiotics (DOX) daunorubicin (DNR), their epimers (EDOX, EDNR) and ten selected analogs is presented. The paper serves as a comprehensive spectral library of UV-vis, IR and Raman spectra of anthracyclines in the solid state and in solution. The particular advantage of Raman spectroscopy for the measurement and analysis of individual antibiotics is demonstrated.
View Article and Find Full Text PDFIn this study, we compared the cellular uptake, intracellular localization and cytotoxicity of two groups of anthracycline derivatives in cultured H9c2(2-1) rat cardiomyoblasts. The first group consisted of doxorubicin (DOX) and two of its derivatives containing a formamidino group (-N = CH-N<) at the C-3' position with a morpholine (DOXM) or a hexamethyleneimine (DOXH) ring. The second group consisted of daunorubicin (DRB) and its derivatives containing a morpholine (DRBM) or a hexamethyleneimine (DRBH) ring.
View Article and Find Full Text PDFBackground/aim: The ability of five formamidinodoxorubicins to induce apoptosis of MCF-7 breast cancer cells was tested. All these compounds were modified at C-3' and contain a formamidine group (-N=CH-NRR), with the rest of the cyclic secondary amine (HNRR) of a gradually increasing ring size.
Materials And Methods: Cytotoxicity was assessed using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.
Background/aim: In this study we investigated the effect of DOX and five of its derivatives containing a formamidine group (NCHNRR) at the 3' position with pyrrolidine (DOX-F PYR), piperidine (DOX-F PIP), morpholine (DOX-F MOR), N-methylpiperazine (DOX-F PAZ) and hexamethyleneimine (DOX-F HEX) ring on SKOV-3 ovarian cancer cells. We have focused on the anti-proliferative activity and the value of apoptosis induced by tested analogues.
Materials And Methods: The following methods were used: spectrophotometric assay with MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide); fluorimetric assays - double staining with Hoechst 33258 and propidium iodide (PI), measurement of caspase-3 activity; flow cytometry methods - phosphatidylserine (PS) externalization using Annexin V-FITC and PI fluorochromes, and TUNEL assay.
Background/aim: Structural modifications of daunorubicin are an important way to change its anticancer activity. For this reason, formamidinodaunorubicins have been synthesized. The present study was undertaken to determine and compare the in vitro effects of daunorubicin and its new formamidine derivatives on human acute leukemia MOLT-4 and ML-1 cells.
View Article and Find Full Text PDFBackground/aim: The comparative effects of daunorubicin, and its new formamidine derivatives containing either a morpholine moiety (DAUFmor) or a hexamethyleneimine moiety (DAUFhex) in the amidine group, on induction of programmed cell death were determined.
Materials And Methods: The experiments were performed on human acute lymphoblastic leukemia MOLT-4 cells and human acute myeloblastic leukemia ML-1 cells. The research was conducted using the flow cytometry annexin V-fluorescein (FITC)/propidium iodide (PI) method and tetramethylrhodamine ethyl ester (TMRE) assay.
Background/aim: In the search for new derivatives of anthracycline antibiotics, formamidinodaunorubicins containing in the amidine group either a morpholine moiety (DAUFmor) or a hexamethyleneimine moiety (DAUFhex) were synthesized. The biological effects of daunorubicin (DAU), DAUFmor and DAUFhex were compared.
Materials And Methods: The experiments were performed on human acute lymphoblastic leukemia MOLT-4 cells and human acute myeloblastic leukemia ML-1 cells.
Oxazolinodoxorubicin, a doxorubicin analog with a modified daunosamine moiety was synthesized. The properties of this compound and the parent doxorubicin were compared. The cytotoxicity in vitro studies against several human tumor cell lines (PC-3, MCF-7, SW707, HL-60, RPMI 8226, ACHN) showed higher antiproliferative potency for this new compound.
View Article and Find Full Text PDFOxazolinodaunorubicin, a new daunorubicin derivative with a modified daunosamine moiety, was synthesized. The biological properties of this derivative and the parent daunorubicin were compared. The results showed antiproliferative activity of the derivative with significantly lower toxicity (an LD(50) value ca.
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