ABSTRACT
1,2,4-Triazoles are privileged scaffolds for many pharmaceuticals, and methods for structurally diverse compound libraries are of current interest. Here we report an efficient coupling of α-diazoacetates with amino acid-derived alkyl N-hydroxy phthalimide esters, under metal-free conditions involving 1,8-diazabicyclo(5.4.0)undec-7-ene as the base, with which highly functionalized 1,2,4-triazoles can be obtained in excellent yields with remarkable functional group tolerance. Preliminary studies revealed that 1,2,4-triazole 3a exhibits potent inhibition of tyrosinase activities in melanoma B16F10 cell lines, demonstrating promising skin-whitening properties.
Subject(s)
Amino Acids , Esters , Triazoles , Animals , Mice , Amino Acids/chemistry , Amino Acids/chemical synthesis , Cycloaddition Reaction , Esters/chemistry , Molecular Structure , Monophenol Monooxygenase/antagonists & inhibitors , Monophenol Monooxygenase/metabolism , Triazoles/chemistry , Triazoles/chemical synthesis , Triazoles/pharmacology , Phthalimides/chemistryABSTRACT
So far, there is still lack of effective treatment to control persistent inflammation immunosuppression catabolism syndrome (PICS) appeared generally in those chronic critical illnesses (CCI) patients, restricted by the development of medicine and scientific research nowadays. Because the uncontrolled PICS aggravates continuously, ICU stay of the CCI patients has been obviously prolonging and the late mortality elevates greatly. So exploring effective therapeutic strategies is obviously pressing. With the characteristics in PICS such as that elderly with sepsis or severe trauma tops the list of morbidity, progressing illness is difficult to intervent and various pathology changes occur simultaneously, the fundamental principle of treatment, "Focal screening, early control, joint intervention" must be followed. As for the specific intervention, lessoning from some diseases with immune and metabolic disorders to take "anabolic nutrition support", is a research focus presently as well as a considerably potential breakthrough at the treatment research in the future. This review retrospects a series of therapeutic strategies of PICS, such as immunity, metabolism regulation, nutrition support, glucose control and physiotherapy, in the purpose of laying the foundation of the development of joint intervention strategy for PICS.
Subject(s)
Immunosuppression Therapy , Inflammation , Nutritional Support , Aged , Critical Illness , Humans , Metabolism , SyndromeABSTRACT
OBJECTIVE: Terminology of persistent inflammation immunosuppression and catabolism syndrome (PICS) is developed based on the concept of multiple organ failure (MOF), which reflect that the preponderance is gradually reversed from pro-inflammation to anti-inflammation, and eventually the state of simultaneously persistent inflammation and severe immunosuppression appeared. Although the improvement of rescue technology and management increase the early survival rates of patient with critical illnesses, the long-term outcomes of most patients are not optimistic. The patients with PICS are difficult to treat or prevent, and are likely to indolent death and have a rising incidence, which is an important challenge to the intensive care unit (ICU). The paper review the understanding of PICS, summarize the specific changes of immune system in PICS, and explore the immunological markers for early recognition of PICS and judgment of immune state in order to provide new thinking for prevention and control of PICS.
Subject(s)
Immunosuppression Therapy , Inflammation , Critical Illness , Humans , Intensive Care Units , Multiple Organ Failure , SyndromeABSTRACT
OBJECTIVE: Sepsis is as life-threatening organ failure caused by a dysregulated host response to infection, with urgent onset, complex mechanism and high mortality. Its early diagnosis and treatment is particularly important. However, the sensitivity and specificity of current laboratory markers for the diagnosis of sepsis is not ideal. MicroRNAs represent a novel group of small RNA molecules that do not encode for proteins. MicroRNAs are synthesized in the cytoplasm and transferred to circulation primarily by micro-vesicles, and they are stable in circulation and can be rapidly detected. The researches regarding circulating miRNA as biomarkers of sepsis were collected to analyze the characteristics of differential expression of miRNAs including miR-150, miR-133a, miR-122, miR-223, miR-4772, miR-297 and miR-574-5p etc. in the pathogenesis of sepsis, which suggest that they can be used as biomarkers for the diagnosis and prognosis of sepsis.
