Design, synthesis and biological evaluation of new embelin derivatives as CK2 Inhibitors

A new series of furan embelin derivatives was synthesized and characterized as ATPcompetitive CK2 inhibitors. The new compounds were efficiently synthesized using a multicomponent approach from embelin (1), aldehydes and isonitriles through a Knoevenagel condensation/ Michael addition/ heterocyclization. Several compounds with inhibitory activities in the low micromolar or even submicromolar were identified. The most active derivative was compound 4l (2-(tert-butylamino)-3-(furan-3-yl)-5- hydroxy-6-undecylbenzofuran-4,7-dione) with an IC50 value of 0.63 μM. It turned out to be an ATP competitive CK2 inhibitor with a Ki value determined to be 0.48 μM. Docking studies allowed the identification of key ligand-CK2 interactions, which could help to further optimize this family of compounds as CK2 inhibitor

Synthesis and Anti-HIV Activity of Lupane and Olean-18-ene Derivatives. Absolute Configuration of 19,20-Epoxylupanes by VCD

Lupane triterpenoids 2 and 5–12 and oleanene derivatives 13 and 14 were prepared from lupeol (1), betulin (3), and germanicol (4). They were tested for anti-HIV activity, and some structure–activity relationships were outlined. The 20-(S) absolute configuration of epoxylupenone (8) was assessed by comparison of the observed and DFT-calculated vibrational circular dichroism spectra. The CompareVOA algorithm was employed to support the C-20 configuration assignment. The 20,29 double bond in lupenone (2) and 3-epilupeol (15) was stereoselectively epoxidized to produce 20-(S)-8 and 20-(S)-16, respectively, an assignment in agreement with their X-ray diffraction structures.Fil: Gutiérrez Nicolás, Fátima. Universidad de la Laguna. Departamento de Química Orgánica. Instituto Universitario de Bio-orgánica "antonio Gonzalez"; España. Instituto Canario de Investigacion del Cáncer; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Bárbara Gordillo, Román. Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional. Departamento de Química; MéxicoFil: Oberti, Juan Carlos María. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina. Universidad de la Laguna. Departamento de Química Orgánica. Instituto Universitario de Bio-orgánica "Antonio Gonzalez"; EspañaFil: Estévez Braun, Ana. Universidad de la Laguna. Departamento de Química Orgánica. Instituto Universitario de Bio-orgánica "antonio Gonzalez"; España. Instituto Canario de Investigación del Cáncer; EspañaFil: Ravelo, Ángel G.. Universidad de la Laguna. Departamento de Química Orgánica. Instituto Universitario de Bio-orgánica "antonio Gonzalez"; España. Instituto Canario de Investigación del Cáncer; EspañaFil: Joseph Nathan, Pedro. Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional. Departamento de Química; Méxic

Epidemiology of surgery associated acute kidney injury (EPIS-AKI): a prospective international observational multi-center clinical study

Purpose: The incidence, patient features, risk factors and outcomes of surgery-associated postoperative acute kidney injury (PO-AKI) across different countries and health care systems is unclear. Methods: We conducted an international prospective, observational, multi-center study in 30 countries in patients undergoing major surgery (> 2-h duration and postoperative intensive care unit (ICU) or high dependency unit admission). The primary endpoint was the occurrence of PO-AKI within 72 h of surgery defined by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Secondary endpoints included PO-AKI severity and duration, use of renal replacement therapy (RRT), mortality, and ICU and hospital length of stay. Results: We studied 10,568 patients and 1945 (18.4%) developed PO-AKI (1236 (63.5%) KDIGO stage 1500 (25.7%) KDIGO stage 2209 (10.7%) KDIGO stage 3). In 33.8% PO-AKI was persistent, and 170/1945 (8.7%) of patients with PO-AKI received RRT in the ICU. Patients with PO-AKI had greater ICU (6.3% vs. 0.7%) and hospital (8.6% vs. 1.4%) mortality, and longer ICU (median 2 (Q1-Q3, 1-3) days vs. 3 (Q1-Q3, 1-6) days) and hospital length of stay (median 14 (Q1-Q3, 9-24) days vs. 10 (Q1-Q3, 7-17) days). Risk factors for PO-AKI included older age, comorbidities (hypertension, diabetes, chronic kidney disease), type, duration and urgency of surgery as well as intraoperative vasopressors, and aminoglycosides administration. Conclusion: In a comprehensive multinational study, approximately one in five patients develop PO-AKI after major surgery. Increasing severity of PO-AKI is associated with a progressive increase in adverse outcomes. Our findings indicate that PO-AKI represents a significant burden for health care worldwide