Formation of β-cyclodextrin complexes in an anhydrous environment

The formation of inclusion complexes of β-cyclodextrin was studied at the melting temperature of guest compounds by differential scanning calorimetry. The complexes of long-chain n-alkanes, polyaromatics, and organic acids were investigated by calorimetry and IR spectroscopy. The complexation ratio of β-cyclodextrin was compared with results obtained in an aqueous environment. The stability and structure of inclusion complexes with various stoichiometries were estimated by quantum chemistry and molecular dynamics calculations. Comparison of experimental and theoretical results confirmed the possible formation of multiple inclusion complexes with guest molecules capable of forming hydrogen bonds. This finding gives new insight into the mechanism of formation of host–guest complexes and shows that hydrophobic interactions play a secondary role in this case. [Figure: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00894-016-3061-6) contains supplementary material, which is available to authorized users

Cytoprotective Effects of Dinitrosyl Iron Complexes on Viability of Human Fibroblasts and Cardiomyocytes

Nitric oxide (NO) is an important signaling molecule that plays a key role in maintaining vascular homeostasis. Dinitrosyl iron complexes (DNICs) generating NO are widely used to treat cardiovascular diseases. However, the involvement of DNICs in the metabolic processes of the cell, their protective properties in doxorubicin-induced toxicity remain to be clarified. Here, we found that novel class of mononuclear DNICs with functional sulfur-containing ligands enhanced the cell viability of human lung fibroblasts and rat cardiomyocytes. Moreover, DNICs demonstrated remarkable protection against doxorubicin-induced toxicity in fibroblasts and in rat cardiomyocytes (H9c2 cells). Data revealed that the DNICs compounds modulate the mitochondria function by decreasing the mitochondrial membrane potential (ΔΨm). Results of flow cytometry showed that DNICs were not affected the proliferation, growth of fibroblasts. In addition, this study showed that DNICs did not affect glutathione levels and the formation of reactive oxygen species in cells. Moreover, results indicated that DNICs maintained the ATP equilibrium in cells. Taken together, these findings show that DNICs have protective properties in vitro. It was further suggested that DNICs may be uncouplers of oxidative phosphorylation in mitochondria and protective mechanism is mainly provided by the leakage of excess charge through the mitochondrial membrane. It is assumed that the DNICs have the therapeutic potential for treating cardiovascular diseases and for decreasing of chemotherapy-induced cardiotoxicity in cancer survivors.</p

Anti-Acanthamoeba Activity of Brominated Sesquiterpenes from Laurencia johnstonii

Focusedonourinteresttodevelopnovelantiparasisticagents,thepresentstudywasaimed to evaluate the biological activity of an extract of Laurencia johnstonii collected in Baja California Sur, Mexico, against an Acantamoeba castellanii Neff strain. Bioassay-guided fractionation allowed us to identify the amoebicidal diastereoisomers α-bromocuparane (4) and α-isobromocuparane (5). Furthermore, bromination of the inactive laurinterol (1) and isolaurinterol (2) yielded four halogenated derivatives, (6)–(9), which improved the activity of the natural sesquiterpenes. Among them, the most active compound was 3α-bromojohnstane (7), a sesquiterpene derivative which possesses a novel carbon skeleton johnstane

Amoebicidal activity of caffeine and maslinic acid by the induction of Programmed Cell Death in Acanthamoeba

International audienceFree-living amoebae of the genus Acanthamoeba are the causal agents of a sight-threatening ulceration of the cornea called Acanthamoeba keratitis, as well as the rare but usually fatal disease granulomatous amoebic encephalitis. Although there are many therapeutic options for the treatment of Acanthamoeba infections, they are generally lengthy and/or have limited efficacy. For the best clinical outcome, treatments should target both the trophozoite and the cyst stages, as cysts are known to confer resistance to treatment. In this study, we document the activities of caffeine and maslinic acid against both the trophozoite and the cyst stages of three clinical strains of Acanthamoeba These drugs were chosen because they are reported to inhibit glycogen phosphorylase, which is required for encystation. Maslinic acid is also reported to be an inhibitor of extracellular proteases, which may be relevant since the protease activities of Acanthamoeba species are correlated with their pathogenicity. We also provide evidence for the first time that both drugs exert their anti-amoebal effects through programmed cell death

First Report of Vermamoeba vermiformis in the Island of El Hierro, Canary Islands, Spain

Background: Free-living amoebae (FLA) are group of protozoa distributed worldwide in many habitats mainly water and soil related sources. Some members of FLA are able to act as opportunistic pathogens and are environmental carriers of other pathogenic agents such as bacteria and viruses. Vermamoeba vermiformis is a highly abundant FLA species in water bodies and has recently gained environmental importance as it acts as a vehicle of many pathogenic bacteria such as Legionella pneumophila.Cases Report: In this study, water samples were collected from the island of El Hierro, Canary Islands, Spain during 2015. El Hierro island was designated by UNESCO as a biosphere reserve and it is currently the less populated of the Canary Islands. The water samples were culture on 2 % Non-Nutrient Agar (NNA) plates covered with a thin layer of heat killed E. coli and checked daily for the presence of FLA. After a week, V. vermiformis amoebae were observed in the plates incubated at room temperature and 37 ºC. Molecular characterization was carried out by amplifying the 18S rDNA gene and DNA sequencing, confirming that the isolated strain belonged to Vermamoeba vermiformis species.Conclusion: To the best of our knowledge, this is the first report of Vermamoeba vermiformis isolation in the island of El Hierro and the second report of this species in the Canary Islands

DNA damage (8-OHdG) and telomere length in captive Psittacidae birds with different longevity

Aging is a complex process influenced by internal and external factors. Oxidative stress damages DNA, leading to 8-hydroxy-2’ deoxyguanosine formation (8-OHdG). Telomere shortening is considered a biomarker of aging and oxidative stress may enhance its attrition. The ability to manage and repair oxidative stress varies among species and life histories. Avian species, such as Psittacidae birds, exhibit exceptional lifespans despite their physiological characteristics that might suggest otherwise. This study investigates 8-OHdG levels in serum samples from long- and short-lived birds of the order Psittaciformes, examining their relationship with telomere length and antioxidant capacity based on lifespan strategies. Among 43 individuals analyzed 26 belonged to the “long-lived species” group and 17 belonged to the “short-lived species” one. Relative telomere length (rTL) was measured in DNA isolated from whole blood by qPCR, and oxidative stress markers, such as Total Antioxidant Capacity (TAC) and 8-OHdG, were determined by spectrophotometry in serum samples. Long-lived birds had longer rTL than short-lived ones [1.308 ± 0.11 vs. 0.565 ± 0.13, (p &lt; 0.001)]. On the contrary, short-lived birds showed more DNA damage than their counterparts [3.847 ± 0.351 vs. 2.012 ± 0.308, respectively, (p &lt; 0.001)]. Old birds had shorter rTL than young ones, for both longevity groups (p &lt; 0.001). Although no correlation was found between 8-OHdG levels and age, nor 8-OHdG and telomere length, long-lived birds exhibited 75.42-unit increased TAC levels when increased 8-OHdG concentrations (p = 0.046). These findings highlight distinct patterns of telomere length and oxidative stress influenced by lifespan strategies among avian longevity groups

Naphthyridine Derivatives Induce Programmed Cell Death in Naegleria fowleri

Primary amoebic encephalitis (PAM) caused by the opportunistic pathogen Naegleria fowleri is characterized as a rapid and lethal infection of the brain which ends in the death of the patient in more than 90% of the reported cases. This amoeba thrives in warm water bodies and causes infection after individuals perform risky activities such as splashing or diving, mostly in non-treated water bodies such as lakes and ponds. Moreover, the infection progresses very fast and no fully effective molecules have currently been found to treat PAM. In this study, naphthyridines fused with chromenes or chromenones previously synthetized by the group were tested in vitro against the trophozoite stage of two strains of N. fowleri. In addition, the most active molecule was evaluated in order to check the induction of programmed cell death (PCD) in the treated amoebae. Compound 3 showed good anti-Naegleria activity (61.45 ± 5.27 and 76.61 ± 10.84 µM, respectively) against the two different strains (ATCC® 30808 and ATCC® 30215) and a good selectivity compared to the cytotoxicity values (>300 µM). In addition, it was able to induce PCD, causing DNA condensation, damage at the cellular membrane, reduction in mitochondrial membrane potential and ATP levels, and ROS generation. Hence, naphthyridines fused with chromenes or chromenones could be potential therapeutic agents against PAM in the near future.This work was funded by PI18/01380 from the Instituto de Salud Carlos III, Spain; RICET (project RD16/0027/0001) from the Programa Redes Temáticas de Investigación Cooperativa, FIS (Ministerio Español de Salud, Madrid, Spain); and CB21/13/00100 Consorcio Centro De Investigacion Biomedica En Red M.P. (CIBER) de Enfermedades Infecciosas, Inst. de Salud Carlos III, Madrid, Spain. A.R.L. and I.A.J. were funded by the Agencia Canaria de Investigación, Innovación y Sociedad de la Información (ACIISI). Additionally, financial support from the Ministerio de Ciencia, Innovación y Universidades (MCIU), Agencia Estatal de Investigación (AEI), and Fondo Europeo de Desarrollo Regional (FEDER; RTI2018-101818-B-I00, UE) and from Gobierno Vasco, Universidad del País Vasco (GV, IT 992-16; UPV) is gratefully acknowledged. Technical and human support provided by IZO-SGI, SGIker (UPV/EHU, MICINN, GV/EJ, ERDF, and ESF) is gratefully acknowledged

An approach to the effects of longevity, sexual maturity, and reproduction on telomere length and oxidative stress in different Psittacidae species

Introduction: Aging is a multifactorial process that includes molecular changes such as telomere shortening. Telomeres shorten progressively with age in vertebrates, and their shortening rate has a significant role in determining the lifespan of a species. However, DNA loss can be enhanced by oxidative stress. The need for novel animal models has recently emerged as a tool to gather more information about the human aging process. Birds live longer than other mammals of the same size, and Psittacidae species are the most persevering of them, due to special key traits.Methods: We aimed to determine telomere length by qPCR, and oxidative stress status using colorimetric and fluorescence methods in different species of the order Psittaciformes with different lifespans.Results: We found that telomeres shorten with age for both long- and short-lived birds (p &lt; 0.001 and p = 0.004, respectively), with long-lived birds presenting longer telomeres than short-lived ones (p = 0.001). In addition, short-lived birds accumulated more oxidative stress products than long-lived birds (p = 0.013), who showed a better antioxidant capacity (p &lt; 0.001). Breeding was found related to telomere shortening in all species (p &lt; 0.001 and p = 0.003 for long- and short-lived birds). Short-lived birds, especially breeding females, increased their oxidative stress products when breeding (p = 0.021), whereas long-lived birds showed greater resistance and even increased their antioxidant capacity (p = 0.002).Conclusion: In conclusion, the relationship between age and telomere length in Psittacidae was verified. The influence of breeding increased cumulative oxidative damage in short-lived species, while long-lived species may counteract this damage

Sesquiterpene lactones as potential therapeutic agents against Naegleria fowleri

Naegleria fowleri is the causative agent the primary amoebic meningoencephalitis (PAM), a fatal disease in more than the 90% of the reported cases that affects the central nervous system. The amoeba infects the nasal cavity of mostly children and young adults who report previous aquatic exposure in warm water sources. The rapid progression of the disease and the lack of effective and safety therapeutic options make the search of new anti-amoebic compounds an urgent issue. In this study, twelve sesquiterpene lactones isolated from the zoanthid Palythoa aff. clavata were tested against the trophozoite stage of Naegleria fowleri. Anhydroartemorin (2) and 1(10)Z,4E,14-acetoxy-costunolide (3) showed the best anti-amoeboid activity values with IC50 23.02 ± 1.26 and 28.34 ± 6.27, respectively. In addition, the mechanisms of programmed cell death induction of these two molecules were evaluated with positive results for both compounds. Finally, a structure-activity relationship was analyzed to reveal the dependence of reactivity and lipophilicity on the biological activity. The log P values of the compounds were calculated to postulate them as good candidates to cross the blood-brain barrier, a limiting factor in the development of new anti-Naegleria treatments. Therefore, the mentioned sesquiterpene lactones could be considered as potential PAM therapeutic options in the future.This work was funded by projects PI18/01380 from Instituto de Salud Carlos III, Spain and RICET (RD16/0027/0001 project) and PID2019–109476RB-C21 (BIOALGRI) (Spanish Ministry of Science, Madrid, Spain; from Programa Redes Temáticas de Investigación Cooperativa, FIS (Ministerio Español de Salud, Madrid, Spain) and FEDER. Consorcio Centro de Investigación Biomédica En Red M.P. (CIBER) de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28006 Madrid, Spain and Cabildo de Tenerife 21/0587 cofunded by MEDI and FDCAN. ARL and IAJ were funded by Agencia Canaria de Investigación, Innovación y Sociedad de la Información (ACIISI). N.N. were funded by the Agustín de Betancourt Programme (Cabildo de Tenerife, TFinnova Programme supported by MEDI and FDCAN funds). Authors acknowledge to Drs. Alberto Brito and Adriana Rodríguez Hernández from Universidad de La Laguna (ULL) the taxonomic classification of biological material, and Dr. Ezequiel Quintana Morales from Instituto de Productos Naturales y Agrobiología, Consejo Superior de Investigaciones Científicas (IPNA-CSIC) for assistance in molecular calculations.Peer reviewe