Potent, selective and reversible hMAO-B inhibition by benzalphthalides: Synthesis, enzymatic and cellular evaluations and virtual docking and predictive studies.

Monoaminooxidases (MAOs) are important targets for drugs used in the treatment of neurological and psychiatric disorders and particularly on Parkinson's Disease (PD). Compounds containing a trans-stilbenoid skeleton have demonstrated good selective and reversible MAO-B inhibition. Here, twenty-two (Z)-3-benzylidenephthalides (benzalphthalides, BPHs) displaying a trans-stilbenoid skeleton have been synthesised and evaluated as inhibitors of the MAO-A and MAO-B isoforms. Some BPHs have selectively inhibited MAO-B, with IC50 values ranging from sub-nM to µM. The most potent compound with IC50 = 0.6 nM was the 3',4'-dichloro-BPH 16, which showed highly selective and reversible MAO-B inhibitory activity. Furthermore, the most selective BPHs displayed a significant protection against the apoptosis, and mitochondrial toxic effects induced by 6-hydroxydopamine (6OHDA) on SH-SY5Y cells, used as a cellular model of PD. The results of virtual binding studies on the most potent compounds docked in MAO-B and MAO-A were in agreement with the potencies and selectivity indexes found experimentally. Additionally, related to toxicity risks, drug-likeness and ADME properties, the predictions found for the most relevant BPHs in this research were within those ranges established for drug candidates.

Synergistic Combination of NAPROC-13 and NMR 13C DFT Calculations: A Powerful Approach for Revising the Structure of Natural Products.

This article describes the structure revision of nine triterpenoids that have been reported corresponding to the same 13C NMR data set. In addition, 13C NMR calculation shows that some chemical shift assignments must be swapped. Our analysis improves the fit between the experimental and calculated data. Correcting misassigned structures and correctly assigning each signal is essential for elucidating new structurally related compounds. Furthermore, the ambiguity of several compounds, the structure of which differs in the literature and the Sci-Finder database, has been eliminated. Misassigned structures were found by chemical shift searches in NAPROC-13, and the results provide two or more different compounds with the same 13C NMR data. The process to determine the correct, most likely structural proposal in agreement with the experimental 13C NMR data was carried out by DFT calculations.

Design and Diversity Analysis of Chemical Libraries in Drug Discovery.

Chemical libraries and compound data sets are among the main inputs to start the drug discovery process at universities, research institutes, and the pharmaceutical industry. The approach used in the design of compound libraries, the chemical information they possess, and the representation of structures, play a fundamental role in the development of studies: chemoinformatics, food informatics, in silico pharmacokinetics, computational toxicology, bioinformatics, and molecular modeling to generate computational hits that will continue the optimization process of drug candidates. The prospects for growth in drug discovery and development processes in chemical, biotechnological, and pharmaceutical companies began a few years ago by integrating computational tools with artificial intelligence methodologies. It is anticipated that it will increase the number of drugs approved by regulatory agencies shortly.

Computational Structural Revision of Elaeophorbate and Other Triterpenoids with the Help of NAPROC-13. A New Strategy for Structural Revision of Natural Products.

A considerable number of natural products have been published in recent years with misassigned structure, even though they had been correctly elucidated in the past. The availability of databases containing revised structures can prevent the amplification of errors in structural elucidation. NAPROC-13, a dereplication tool based on the 13C chemical shift, has been used to search for substances that, possessing the same chemical shifts, have been described with different structures. The correct structure of these different structural proposals is verified by computational chemistry. This paper reports the structural revision of nine triterpenoids following this methodology.

A new host-targeted antiviral cyclolignan (SAU-22.107) for Dengue Virus infection in cell cultures. Potential action mechanisms based on cell imaging.

Dengue virus (DENV) infection is the most arbovirosis in the world. However, medications have not been approved for its treatment. Drug discovery based on the host-targeted antiviral (HTA) constitutes a new promising strategy, considering their high genetic barrier to resistance and the low probability of selecting drug resistance strains. In this study, we have tested fifty-seven podophyllotoxin-related cyclolignans on DENV-2 infected cells and found the most promising compound was S.71. Using cellular and molecular biology experiments, we have discovered that the new lignan altered the distribution of microtubules, induced changes in cell morphology, and caused retraction of the rough endoplasmic reticulum. In addition, the compound alters the viral envelope protein and the double-stranded RNA, while there is a decrease in negative-strand RNA synthesis; especially when the compound was added between 6- and 12-hours post-infection. Altogether, S.71 decreases the viral yield through an HTA-related mechanism of action, possibly altering the DENV genome replication and/or polyprotein translation, through the alteration of microtubule distribution and endoplasmic reticulum deterioration. Finally, pharmacokinetic predictors show that S.71 falls within the standard ranges established for drugs.

Effects of Thiamethoxam-Dressed Oilseed Rape Seeds and Nosema ceranae on Colonies of Apis mellifera iberiensis, L. under Field Conditions of Central Spain. Is Hormesis Playing a Role?

To study the influence of thiamethoxam exposure on colony strength and pathogen prevalence, an apiary (5 colonies) was placed in front of a plot sown with winter oilseed rape (wOSR), just before the flowering phase. Before sowing, the seeds were treated with an equivalent application of 18 g thiamethoxam/ha. For comparison, a second apiary (5 colonies) was located in front of a separate 750 m plot sown with untreated wOSR. Dead foragers at the entrance of hives were assessed every 2-3 days throughout the exposure period, while the colony strength (number of combs covered with adult honey bees and brood) and pathogens were monitored each month until the following spring. Foraging on the wOSR crop was confirmed by melissopalynology determination of the corbicular pollen collected periodically, while the chemical analysis showed that exposure to thiamethoxam was mainly through nectar. There was an increase in the accumulation of dead bees in the apiary exposed to thiamethoxam relating with the control, which was coped with an increment of bee brood surface and adult bee population. However, we did not find statistically significant differences between apiaries (α = 0.05) in terms of the evolution of pathogens. We discuss these results under hormesis perspective.

New Cable Delay Measurement System for VGOS Stations.

This paper presents the new cable delay measurement system (CDMS) designed at Yebes Observatory (IGN, Spain), which is required for the VLBI Global Observing System (VGOS) stations. This system measures the phase difference between the 5 MHz reference signal from the hydrogen maser and the 5 MHz signal that reaches the broadband receiver through a coaxial cable, for the generation of calibration tones. As a result, the system detects the changes in the length of that coaxial cable due to temperature variations along the cable run and flexures caused by VGOS radio telescope movements. This CDMS outperforms the previous versions: firstly, it does not require a frequency counter for phase/delay measurements; secondly, it largely reduces the use of digital circuits; hence, reducing digital noise; and thirdly, it has a remotely controlled automatic calibration subsystem. The system was tested in the laboratory and in the radio telescope, and the measurements of both set-ups are shown. These measurements include the total noise, accuracy, hysteresis, and stability. The results in the radio telescope can be correlated with the different factors that affect the cable, such as temperature and flexures. The system allows to achieve an RMS noise of less than 0.5 ps, significantly improving the requirements established in VGOS. The system is currently installed in the Red Atlántica de Estaciones Geodinámicas y Espaciales (RAEGE)Yebes VGOS 13.2 m radio telescope, and will be installed in the Norwegian Mapping Authority (NMA) twin VGOS radio telescopes, in the Finnish Geospatial Research Institute (FGI) VGOS station and in the RAEGE Santa María VGOS radio telescope (Açores, Portugal).

Anthelmintic activity of aminoalcohol and diamine derivatives against the gastrointestinal nematode Teladorsagia circumcincta.

Gastrointestinal nematodes (GIN) infections are a serious problem in livestock production due to the great economic losses they cause. Their control is increasingly difficult because of the rapid development of drug resistance and the limited number of available drugs. Therefore, this study evaluated 18 aminoalcohol and 16 diamine derivatives against eggs, first and third stage larvae from a susceptible and a resistant isolate of Teladorsagia circumcincta collected from sheep. The effectiveness of the in vitro anthelmintic activity of the compounds was evaluated using three different procedures: Egg Hatch Test (EHT), Larval Mortality Test (LMT) and Larval Migration Inhibition Test (LMIT). Those compounds with activities higher than 90 % in the initial screening at 50 µM were selected to determine their half maximal effective concentration (EC50). In parallel, cytotoxicity assays were conducted on Caco2 and HepG2 cell lines to calculate Selectivity Indexes (SI) for each compound. The diamine 30 presented the best results in preventing egg hatching, displaying the lowest EC50 value (1.01 ±â€¯0.04 µM) of all compounds tested and the highest SI (21.21 vs. Caco-2 cells). For the LMIT, the diamine 34 showed the highest efficacy, with EC50 values of 2.67 ±â€¯0.08 and 3.02 ±â€¯0.09 µM on the susceptible and resistant isolate of the parasite, respectively.

A Tri-Band Cooled Receiver for Geodetic VLBI.

This paper shows a simultaneous tri-band (S: 2.2-2.7 GHz, X: 7.5-9 GHz and Ka: 28-33 GHz) low-noise cryogenic receiver for geodetic Very Long Baseline Interferometry (geo-VLBI) which has been developed at Yebes Observatory laboratories in Spain. A special feature is that the whole receiver front-end is fully coolable down to cryogenic temperatures to minimize receiver noise. It was installed in the first radio telescope of the Red Atlántica de Estaciones Geodinámicas y Espaciales (RAEGE) project, which is located in Yebes Observatory, in the frame of the VLBI Global Observing System (VGOS). After this, the receiver was borrowed by the Norwegian Mapping Autorithy (NMA) for the commissioning of two VGOS radiotelescopes in Svalbard (Norway). A second identical receiver was built for the Ishioka VGOS station of the Geospatial Information Authority (GSI) of Japan, and a third one for the second RAEGE VGOS station, located in Santa María (Açores Archipelago, Portugal). The average receiver noise temperatures are 21, 23, and 25 Kelvin and the measured antenna efficiencies are 70%, 75%, and 60% in S-band, X-band, and Ka-band, respectively.

Synthesis of Cannabinoids: "In Water" and "On Water" Approaches: Influence of SDS Micelles.

We have proven that the biomimetic-like synthesis of cannabinoids from citral and the corresponding phenolic counterpart may well be carried out using water as a solvent. The influence of different additives such as surfactants was also analyzed. Rationalization of the reaction mode and regiochemistry of the processes were provided in terms of "on water" and "in water" reactions. The same reactions were conducted in organic media using Ga(III) salts as catalysts. Worthy of being underlined, an unprecedented formal [2+2+2] process was found to occur between two citral molecules and the corresponding phenolic species in both aqueous and organic environments. Computational studies were performed in order to gain a comprehensive mechanistic and energetic understanding of the different steps of this singular process. Finally, the influence of SDS micelles in the chemical behavior of olivetol and citral was also pursued using PGSE diffusion and NOESY NMR studies. These data permitted to tentatively propose the existence of a mixed micelle between olivetol and SDS assemblies.

Validación aparente de un Instrumento para la Notificación de Eventos Adversos Asociados a la Atención de la Salud / Apparent validation of a Health Care Adverse Event Notification Instrument

Resumen El objetivo de este estudio fue validar la apariencia de un instrumento de notificación de eventos adversos (EA) basado en el "Sistema de Notificación y Aprendizaje para la Seguridad del Paciente" propuesto por el Ministerio de Sanidad Español, desde la percepción de enfermeras y enfermeros de las Áreas de Medicinas y Cirugías del Hospital Rafael Ángel Calderón Guardia durante el I semestre del año 2017. A partir de un diseño cualitativo, participaron en la validación aparente del instrumento 15 enfermeros(as). No se registraron aportes en cuanto a la redacción y la secuencia lógica de la información. Se agregaron tres ítemes. Lo anterior, al considerar que las ideas expresadas estuvieran en concordancia con los principios de voluntariedad de la notificación, la no punibilidad, la confidencialidad, la orientación sistémica, la promoción del análisis para el aprendizaje y la implementación de mejoras. Se concluye que el instrumento es considerado adecuado para la notificación de eventos adversos asociados a la atención de la salud en dicho centro hospitalario.

Abstract The objective of this study was to validate the appearance of an adverse event notification (EA) instrument based on the "System of Notification and Learning for Patient Safety" proposed by the Spanish Ministry of Health, from the perception of nurses of the Medicine and Surgery Areas of the Rafael Ángel Calderón Guardia Hospital during the first semester of 2017. Based on a qualitative design, 15 nurses participated in the apparent validation of the instrument. No contributions were recorded regarding the writing and logical sequence of the information. Three items were added. The foregoing, considering that the ideas expressed were in accordance with the principles of voluntary reporting, non-punishability, confidentiality, systemic orientation, promotion of analysis for learning and implementation of improvements. It is concluded that the instrument is considered adequate for the notification of adverse events associated with health care in that hospital center.

Resumo O objetivo deste estudo foi validar o aparecimento de um instrumento de notificação de eventos adversos (EA) baseado no "Sistema de Notificação e Aprendizado para Segurança do Paciente" proposto pelo Ministério da Saúde da Espanha, a partir da percepção dos enfermeiros. das Áreas de Medicina e Cirurgia do Hospital Rafael Ángel Calderón Guardia durante o primeiro semestre de 2017. Com base em um desenho qualitativo, 15 enfermeiros participaram da aparente validação do instrumento. Não foram registradas contribuições quanto à escrita e sequência lógica das informações. Três itens foram adicionados. O exposto, considerando que as idéias expressas estavam de acordo com os princípios de denúncia voluntária, não punibilidade, confidencialidade, orientação sistêmica, promoção de análises para aprendizado e implementação de melhorias. Conclui-se que o instrumento é considerado adequado para a notificação de eventos adversos associados aos cuidados de saúde naquele centro hospitalar.

Synthesis, bioevaluation and docking studies of some 2-phenyl-1H-benzimidazole derivatives as anthelminthic agents against the nematode Teladorsagia circumcincta.

Gastrointestinal nematode infections are the main diseases in herds of small ruminants. Resistance to the main established drugs has become a worldwide problem. The purpose of this study is to obtain and evaluate the in vitro ovicidal and larvicidal activity of some 2-phenylbenzimidazole derivatives on susceptible and resistant strains of Teladorsagia circumcincta. Compounds were prepared by known procedures from substituted o-phenylenediamines and arylaldehydes or intermediate sodium 1-hydroxyphenylmethanesulfonate derivatives. Egg Hatch Test (EHT), Larval Mortality Test (LMT) and Larval Migration Inhibition Test (LMIT) were used in the initial screening of compounds at 50 µM concentration, and EC50 values were determined for the most potent compounds. Cytotoxicity evaluation of compounds was conducted on human Caco-2 and HepG2 cell lines to calculate their Selectivity Indexes (SI). At 50 µM concentration, nine out of twenty-four compounds displayed more than 98% ovicidal activity on a susceptible strain, and four of them showed more than 86% on one resistant strain. The most potent ovicidal benzimidazole (BZ) 3 showed EC50 = 6.30 µM, for the susceptible strain, while BZ 2 showed the lowest EC50 value of 14.5 µM for the resistant strain. Docking studies of most potent compounds in a modelled Teladorsagia tubulin indicated an inverted orientation for BZ 1 in the colchicine binding site, probably due to its fair interaction with glutamic acid at codon 198, which could justify its inactivity against the resistant strain of T. circumcincta.

Mimicking Halimane Synthases: Monitoring a Cascade of Cyclizations and Rearrangements from Epoxypolyprenes.

We have developed and rationalized a biomimetic transformation mimicking halimane synthases based on a Lewis acid-catalyzed cascade of cyclizations and rearrangements of epoxypolyprenes. Two rings, three stereogenic centers, and a new double bond were generated in a single chemical operation. Based on this cascade transformation, we achieved a unified strategy toward the stereoselective total syntheses of halimene-type terpenoids and analogues as a proof-of-concept study. This method has been applied to the rapid synthesis of diterpene isotuberculosinol, a virulence factor of Mycobacterium tuberculosis as a representative example.

Germacrone Derivatives as new Insecticidal and Acaricidal Compounds: A Structure-Activity Relationship.

Currently, the use of synthetic pesticides is the main method of plant protection applied in agri- and horticulture. However, its excessive use leads to the development of pesticide resistance, a contamination of the environment, toxicity to non-target organisms, and risks for human health. With the ultimate aim of contributing to the develop of a more sustainable pest management, we used the natural product germacrone (compound 1), reported to possess significant insecticidal activity, as starting material for the generation of molecular diversity (2-24). Some of the generated derivatives are natural compounds, such as 1,10-epoxygermacrone (2), 4,5-epoxygermacrone (3), gajutsulactone A (7), germacrol (11), isogermacrone (14), 9-hydroxyeudesma-3,7(11)dien-6-one (19), eudesma-4,7(11),dien-8-one (20), eudesma-3,7(11)-dien-8-one (21) and eudesma-4(15),7(11)-dien-8-one (22). Compounds, 7,11-9,10-diepoxigermacr-4,5-en-8-ol (17), 7,11-epoxieudesma-4,7(11)-dien-8-one (23) and 7,11-epoxieudesma-3,7(11)-dien-8-one (24) are described for the first time. The biocidal activity of most of these compounds was assayed against the tick Hyalomma lusitanicum. The acaricidal effects of compound 24 were four times higher than that of germacrone (1). Compound 2 is an insect antifeedant a thousand times more potent than germacrone against Rhopalosiphum padi, which makes this substance a promising selective antifeedant against this cereal pest.

Assessment of the antinociceptive and anti-inflammatory activities of the stem methanol extract of Diplotropis purpurea.

Context: Since there is still a great need to search for plant species with antinociceptive and anti-inflammatory activities, Diploptropis purpurea (Rich.) Amshoff (Fabaceae) is studied for the first time. Objective: This evaluates the analgesic and anti-inflammatory activities of the stem methanol extract of Diplotropis purpurea (MEDP). Material and methods: The anti-inflammatory and analgesic effects of MEDP of D. purpurea were evaluated in vivo. The antinociceptive activity was assessed in CD1 male mice were treated by oral gavage with 500 mg/kg of MEDP 30 min before submitting to acetic acid-induced abdominal writhing, hot-plate, and formalin tests. Paws oedema induced by carrageenan, histamine or serotonin were performed in male Sprague-Dawley rats to determinate the anti-inflammatory activity. Results: Oral administration of MEDP produced significant antinociceptive effects on the inflammatory phase in the formalin test [12.0 s versus 72.5 s in carboxymethyl cellulose (CMC) control group]. MEDP produced an analgesic effect in the hot-plate model, although the effect was modest compared to tramadol (40 and 60%, respectively). The oral administration of MEDP in a dose of 500 mg/kg showed maximum inhibition (75.1%) after 0.5 h in carrageenan-induced oedema, but it did not modify histamine or serotonin-induced oedemas. Discussion and conclusion: In the peripheral nociception model, acetic acid-induced abdominal writhing, the MEDP did not show a protective effect, but its analgesic effects were evident in the inflammatory phase of the formalin test and in the hot-plate model. These results show that the anti-inflammatory effect was accompanied by a reduction in the perception of painful stimuli.

15-Hydroxygermacranolides as Sources of Structural Diversity: Synthesis of Sesquiterpene Lactones by Cyclization and Rearrangement Reactions. Experimental and DFT Study.

A study on the electrophile-induced rearrangement of two 15-hydroxygermacranolides, salonitenolide and artemisiifolin, was carried out. These compounds underwent electrophilic intramolecular cyclizations or acid-mediated rearrangements to give sesquiterpene lactones with different skeletons such as eudesmanolides, guaianolides, amorphanolides, or other germacranolides. The cyclization that gives guaianolides can be considered a biomimetic route to this type of sesquiterpene lactones. The use of acetone as a solvent changes the reactivity of the two starting germacranolides to the acid catalysts, with a 4,15-diol acetonide being the main product obtained. The δ-amorphenolide obtained by intramolecular cyclization of this acetonide is a valuable intermediate for accessing the antimalarials artemisinin and its derivatives. Mechanistic proposals for the transformations are raised, and to provide support them, quantum chemical calculations [DFT B3LYP/6-31+G(d,p) level] were undertaken.

Antileishmanial activity and tubulin polymerization inhibition of podophyllotoxin derivatives on Leishmania infantum.

Leishmania microtubules play an important role not only in cell division, but also in keeping the shape of the parasite and motility of its free-living stages. Microtubules result from the self-assembly of alpha and beta tubulins, two phylogenetically conserved and very abundant eukaryotic proteins in kinetoplastids. The colchicine binding domain has inspired the discovery and development of several drugs currently in clinical use against parasites. However, this domain is less conserved in kinetoplastids and may be selectively targeted by new compounds. This report shows the antileishmanial effect of several series of compounds (53), derived from podophyllotoxin (a natural cyclolignan isolated from rhizomes of Podophyllum spp.) and podophyllic aldehyde, on a transgenic, fluorescence-emitting strain of Leishmania infantum. These compounds were tested on both promastigotes and amastigote-infected mouse splenocytes, and in mammalian - mouse non-infected splenocytes and liver HepG2 cells - in order to determine selective indexes of the drugs. Results obtained with podophyllotoxin derivatives showed that the hydroxyl group at position C-7α was a structural requisite to kill the parasites. On regards podophyllic aldehyde, derivatives with C9-aldehyde group integrated into a bicyclic heterostructure displayed more potent antileishmanial effects and were relatively safe for host cells. Docking studies of podophyllotoxin and podophyllic aldehyde derivatives showed that these compounds share a similar pattern of interaction at the colchicine site of Leishmania tubulin, thus pointing to a common mechanism of action. However, the results obtained suggested that despite tubulin is a remarkable target against leishmaniasis, there is a poor correlation between inhibition of tubulin polymerization and antileishmanial effect of many of the compounds tested, fact that points to alternative pathways to kill the parasites.

A DFT-Based Computational-Experimental Methodology for Synthetic Chemistry: Example of Application to the Catalytic Opening of Epoxides by Titanocene.

A novel DFT-based Reaction Kinetics (DFT-RK) simulation approach, employed in combination with real-time data from reaction monitoring instrumentation (like UV-vis, FTIR, Raman, and 2D NMR benchtop spectrometers), is shown to provide a detailed methodology for the analysis and design of complex synthetic chemistry schemes. As an example, it is applied to the opening of epoxides by titanocene in THF, a catalytic system with abundant experimental data available. Through a DFT-RK analysis of real-time IR data, we have developed a comprehensive mechanistic model that opens new perspectives to understand previous experiments. Although derived specifically from the opening of epoxides, the prediction capabilities of the model, built on elementary reactions, together with its practical side (reaction kinetics simulations of real experimental conditions) make it a useful simulation tool for the design of new experiments, as well as for the conception and development of improved versions of the reagents. From the perspective of the methodology employed, because both the computational (DFT-RK) and the experimental (spectroscopic data) components can follow the time evolution of several species simultaneously, it is expected to provide a helpful tool for the study of complex systems in synthetic chemistry.

Neoflavonoids as Inhibitors of HIV-1 Replication by Targeting the Tat and NF-κB Pathways.

Twenty-eight neoflavonoids have been prepared and evaluated in vitro against HIV-1. Antiviral activity was assessed on MT-2 cells infected with viral clones carrying the luciferase reporter gene. Inhibition of HIV transcription and Tat function were tested on cells stably transfected with the HIV-LTR and Tat protein. Seven 4-phenylchromen-2-one derivatives showed HIV transcriptional inhibitory activity but only the phenylchrome-2-one 10 inhibited NF-κB and displayed anti-Tat activity simultaneously. Compounds 10, 14, and 25, inhibited HIV replication in both targets at concentrations <25 µM. The assays of these synthetic 4-phenylchromen-2-ones may aid in the investigation of some aspects of the anti-HIV activity of such compounds and could serve as a scaffold for designing better anti-HIV compounds, which may lead to a potential anti-HIV therapeutic drug.

[Leiomyosarcoma of the inferior vena cava. Case report and literature review]. / Leiomiosarcoma de vena cava inferior. Caso clínico y revisión bibliográfica.

BACKGROUND: Large vessel sarcomas are rare tumours. Leiomyosarcoma of the inferior vena cava is the most common. About 300 cases have been reported in the literature. They tend to be large, and not develop metastasis. The prognosis of these tumours is poor. CLINICAL CASE: An 81 year-old woman who complained of pain in the right flank, with no other symptoms. Abdominal computed tomography showed a large retroperitoneal mass, which affected the inferior vena cava, with signs of thrombosis inside. It also encompassed the right renal vein and the right kidney. Excision of the tumour was performed in block, performing an autologous saphenous vein bypass between left the renal vein and proximal segment of inferior vena cava. DISCUSSION: Leiomyosarcomas of the inferior vena cava are classified according to their relationship with adjacent structures. The clinical signs and symptoms are generally non-specific. Diagnosis is made using computed tomography or magnetic resonance imaging, and biopsy of the retroperitoneal mass. Surgery is the only treatment capable of providing prolonged survival. The surgical management is determined by: the level of involvement, the extension, and the presence or absence of collateral veins. The role of adjuvant therapy is controversial. CONCLUSIONS: Inferior vena cava leiomyosarcomas remain a challenge for surgeons. At present, radical resection with negative margins, offers the highest survival rate. The best results are obtained with a multidisciplinary approach by experienced teams in the management of these tumours.