ABSTRACT
Leukemia is the most common blood cancer, and its development starts at diverse points, leading to distinct subtypes that respond differently to therapy. This heterogeneity is rarely taken into account in therapies, so it is still essential to look for new specific drugs for leukemia subtypes or even for therapy-resistant cases. Naphthoquinones (NQ) are considered privileged structures in medicinal chemistry due to their plethora of biological activities, including antimicrobial and anticancer effects. Nitrogen-containing heterocycles such as 1,2,3-1H-triazoles have been identified as general scaffolds for generating glycosidase inhibitors. In the present study, the NQ and 1,2,3-1H-triazole cores have been combined to chemically synthesize 18 new 1,2-furanonaphthoquinones tethered to 1,2,3-1H-triazoles (1,2-FNQT). Their cytotoxicities were evaluated against four different leukemia cell lines, including MOLT-4 and CEM (lymphoid cell lines) and K562 and KG1 (myeloid cell lines), as well as normal human peripheral blood mononucleated cells (PBMCs). The new 1,2-FNQT series showed high cytotoxic potential against all leukemia cell lines tested, and some compounds (12o and 12p) showed even better results than the classical therapeutic compounds such as doxorubicin or cisplatin. Others compounds, such as 12b, are promising because of their high selectivity against lymphoblastic leukemia and their low activity against normal hematopoietic cells. The cells of lymphoid origin (MOLT and CEM) were generally more sensitive than the myeloid cell lines to this series of compounds, and most of the compounds that showed the highest cytotoxicity were similarly active against both cell lines.
Subject(s)
Furans/chemical synthesis , Furans/pharmacology , Leukemia, Lymphoid/pathology , Leukemia, Myeloid/pathology , Naphthoquinones/chemical synthesis , Naphthoquinones/pharmacology , Triazoles/chemistry , Triazoles/pharmacology , Cell Line, Tumor , Cell Survival/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Furans/chemistry , Humans , K562 Cells , Leukemia, Lymphoid/drug therapy , Leukemia, Myeloid/drug therapy , Molecular Structure , Naphthoquinones/chemistry , Structure-Activity RelationshipABSTRACT
No disponible
Subject(s)
Humans , Female , Aged , Hepatitis C, Chronic/complications , Renal Dialysis , Renal Insufficiency, Chronic/complications , Nephritis, Hereditary/therapy , Kidney TransplantationSubject(s)
Antiviral Agents/therapeutic use , Hepatitis C, Chronic/drug therapy , Interferon-alpha/therapeutic use , Kidney Failure, Chronic/therapy , Polyethylene Glycols/therapeutic use , Renal Dialysis , Ribavirin/therapeutic use , Aged , Female , Hepatitis C, Chronic/complications , Humans , Kidney Failure, Chronic/complications , Recombinant Proteins/therapeutic useABSTRACT
Las peritonitis son las infecciones más problemáticas en los pacientes sometidos a diálisis peritoneal, puesto que pueden llegar a comprometer la técnica. Actualmente el tratamiento incluye tratamiento empírico con vancomicina, cefalosporinas y aminoglucósidos hasta conocer el causante de dicha infección. Pero la realidad microbiológica, en cuanto a emergencia de resistencias, hace necesaria la incorporación de nuevos fármacos al arsenal terapéutico para tratar las peritonitis complicadas que pueden convertirse en recurrentes y comprometer la eficacia de la membrana. La daptomicina es un antibiótico lipopeptídico que se utiliza para el tratamiento de infecciones por bacterias grampositivas. No tiene aprobada la indicación en el tratamiento de este tipo de infecciones, pero está comenzando a utilizarse en este campo debido a su elevada efectividad ante infecciones por bacterias resistentes a meticilina con sensibilidades intermedias a vancomicina, sobre todo cuando se asocian a la presencia de un biofilm (AU)
Forms of peritonitis are the most problematic infections in patients undergoing peritoneal dialysis since they can jeopardise the technique. Current treatment includes administering vancomycin, cephalosporins and aminoglycosides empirically until the cause of the infection is known. However, the current situation with regard to emerging bacterial resistances makes it necessary to include new drugs in the therapeutic array for complicated forms of peritonitis that may become recurrent and compromise dialyser efficacy. Daptomycin is a lipopeptide antibiotic used to treat gram-positive bacterial infections. It has not yet been approved for treatment of infections of this type, but it is starting to be used in this area due to being highly effective against methicillin-resistant bacteria with intermediate sensitivity to vancomycin, particularly when the bacteria are associated with biofilm formation (AU)
Subject(s)
Humans , Daptomycin/administration & dosage , Peritonitis/drug therapy , Catheter-Related Infections/drug therapy , Peritoneal Dialysis/adverse effects , Infusions, Parenteral/methods , BiofilmsABSTRACT
Forms of peritonitis are the most problematic infections in patients undergoing peritoneal dialysis since they can jeopardise the technique. Current treatment includes administering vancomycin, cephalosporins and aminoglycosides empirically until the cause of the infection is known. However, the current situation with regard to emerging bacterial resistances makes it necessary to include new drugs in the therapeutic array for complicated forms of peritonitis that may become recurrent and compromise dialyser efficacy. Daptomycin is a lipopeptide antibiotic used to treat gram-positive bacterial infections. It has not yet been approved for treatment of infections of this type, but it is starting to be used in this area due to being highly effective against methicillin-resistant bacteria with intermediate sensitivity to vancomycin, particularly when the bacteria are associated with biofilm formation.
Subject(s)
Anti-Bacterial Agents/administration & dosage , Bacterial Physiological Phenomena , Biofilms , Daptomycin/administration & dosage , Peritonitis/drug therapy , Peritonitis/microbiology , Humans , Injections, Intraperitoneal , RecurrenceSubject(s)
Angiogenesis Inhibitors/adverse effects , Antibodies, Monoclonal, Humanized/adverse effects , Atrial Fibrillation/complications , Intracranial Embolism/etiology , Macular Degeneration/drug therapy , Thrombophilia/chemically induced , Acenocoumarol/administration & dosage , Acenocoumarol/therapeutic use , Aged, 80 and over , Angiogenesis Inhibitors/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Anticoagulants/administration & dosage , Anticoagulants/therapeutic use , Bronchitis/complications , Disease Susceptibility , Drug Therapy, Combination , Enoxaparin/administration & dosage , Enoxaparin/therapeutic use , Heart Failure/complications , Humans , Hypertension/complications , Intracranial Embolism/chemically induced , Male , Ranibizumab , Risk , Thrombophilia/drug therapySubject(s)
Antineoplastic Agents/adverse effects , Dihydropyrimidine Dehydrogenase Deficiency/physiopathology , Fluorouracil/adverse effects , Antineoplastic Agents/therapeutic use , Dihydropyrimidine Dehydrogenase Deficiency/complications , Drug-Related Side Effects and Adverse Reactions/chemically induced , Drug-Related Side Effects and Adverse Reactions/diagnosis , Fluorouracil/therapeutic use , Humans , Male , Middle Aged , Severity of Illness Index , Sigmoid Neoplasms/complications , Sigmoid Neoplasms/drug therapyABSTRACT
No disponible
Subject(s)
Humans , Male , Middle Aged , Fluorouracil/toxicity , Oxidoreductases/deficiency , Rectal Neoplasms/drug therapyABSTRACT
We used a group of lectins (Con-A, WGA, SBA, DBA, RCA-1, UEA-1), enzymes (neuraminidase digestion) and conventional histochemical techniques (periodic acid-Schiff reaction and reduction-saponification-Schiff reaction) in order to detect the presence of glycoproteins rich in sialic and neuraminic acids in the human eccrine sweat glands. Using both identification systems, our results showed an abundant secretion, rich in C8Oxi-acylated sialic acid.