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

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

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

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

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 < 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 < 0.001). Breeding was found related to telomere shortening in all species (p < 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

Gongolarones as antiamoeboid chemical scaffold

Free Living Amoeba (FLA) infections caused by Acanthamoeba genus include chronic nervous system diseases such as Granulomatous Amoebic Encephalitis (GAE), or a severe eye infection known as Acanthamoeba keratitis (AK). Current studies focused on therapy against these diseases are aiming to find novel compounds with amoebicidal activity and low toxicity to human tissues. Brown algae, such as Gongolaria abies-marina (previously known as Cystoseira abies-marina, S.G. Gmelin), presents bioactive molecules of interest, including some with antiprotozoal activity. In this study, six meroterpenoids were isolated and purified from the species Gongolaria abies-marina. Gongolarones A (1), B (2) and C (3) were identified as new compounds. Additionally, cystomexicone B (4), 1′-methoxyamentadione (5) and 6Z-1′-methoxyamentadione (6) were isolated. All compounds exhibited amoebicidal activity against Acanthamoeba castellanii Neff, A. polyphaga and A. griffini strains. Gongolarones A (1) and C (3) showed the lowest IC50 values against the two stages of these amoebae (trophozoite and cyst). Structure-activity relationship revealed that the cyclization by ether formation from C-12 to C-15 of 1, and the isomerization Δ2 t to Δ3 t of 3, increased the antiamoeboid activity of both compounds. Furthermore, gongolarones A (1) and C (3) triggered chromatin condensation, mitochondrial malfunction, oxidative stress, and disorganization of the tubulin-actin cytoskeleton in treated trophozoites. Moreover, transmission electron microscopy (TEM) images analysis revealed that compounds 1 and 3 induced autophagy process and inhibited the encystation process. All those results suggest that both compounds could induce programmed cell death (PCD) in Acanthamoeba.This study was supported funded by projects PID2019-109476RB-C21 (BIOALGRI) (Spanish Ministry of Science), Madrid, Spain; Fundación CajaCanarias–Fundación Bancaria “La Caixa” (2019SP52). Red de Investigación Cooperativa en Enfermedades Tropicales (RICET), Spain (project no. RD16/0027/0001 of the programe of Redes Temáticas de Investigación Cooperativa, FIS). Consorcio Centro de Investigación Biomédica en Red (CIBER), Área de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28029, Madrid, Spain (CB21/13/00100). Project No. 21/0587 funded by the Cabildo de Tenerife, Tenerife innova, Marco Estratégico de Desarrollo Insular (MEDI) and Fondo de Desarrollo de Canarias (FDCAN). Project number ProID2021010118 funded by Agencia Canaria de Investigación, Innovación y Sociedad de la Información (ACIISI). RLRE was funded by a grant from ACIISI cofunded by Fondo Social Europeo (FSE) and FEDER, (TESIS2020010117). MOM was supported by the Programa de Apoyos para la Superación del Personal Académico de la UNAM (PASPA 2021) for carrying out the research stay between the Universidad de La Laguna and la Facultad de Estudios Superiores Iztacala.Peer reviewe