Synthesis of novel fluoro phenyl triazoles via click chemistry with or without microwave irradiation and their evaluation as anti-proliferative agents in SiHa cells.

AIMS: Perform the synthesis of novel fluoro phenyl triazoles via click chemistry with or without microwave irradiation and their evaluation as anti-proliferative agents in SiHa cells Background: Triazoles are heterocyclic compounds containing a five-member ring with two carbon and three nitrogen atoms. They are of great importance since many of them have shown to have biological activity as antifungal, antiviral, antibacterial, anti-HIV, anti-tuberculosis, vasodilator, and anticancer agents. OBJECTIVE: Synthesize novel fluoro phenyl triazoles via click chemistry and evaluate their anti-proliferative activity Method: First, several fluorophenyl azides were prepared. Reacting these aryl azides with phenylacetylene in the presence of Cu(I) catalyst, the corresponding fluoro phenyl triazoles were obtained by two methodologies, stirring at room temperature and under microwave irradiation at 40 ºC. In addition, their antiproliferative activity was evaluated in cervical cancer SiHa cells Result: Fluoro phenyl triazoles were obtained within minutes by means of microwave irradiation. The compound 3f, containing two fluorine atoms next to the carbon connected to the triazole ring, was the most potent among the fluoro phenyl triazoles tested in this study. Interestingly, the addition of a fluorine atom to the phenyl triazole structure in a specific site increases its antiproliferative effect as compared to parent phenyl triazole 3a without a fluorine atom. CONCLUSION: Several fluoro phenyl triazoles were obtained by reacting fluoro phenyl azides with phenylacetylene in the presence of copper sulphate, sodium ascorbate and phenanthroline. Preparation of these triazoles with MW irradiation represents a better methodology since they are obtained within minutes and higher yields of cleaner compounds are obtained. In terms of biological studies, the proximity between fluorine atom and triazole ring increases its biological activity.

The Relevance and Insights on 1,4-Naphthoquinones as Antimicrobial and Antitumoral Molecules: A Systematic Review.

Natural product derivatives are essential in searching for compounds with important chemical, biological, and medical applications. Naphthoquinones are secondary metabolites found in plants and are used in traditional medicine to treat diverse human diseases. Considering this, the synthesis of naphthoquinone derivatives has been explored to contain compounds with potential biological activity. It has been reported that the chemical modification of naphthoquinones improves their pharmacological properties by introducing amines, amino acids, furan, pyran, pyrazole, triazole, indole, among other chemical groups. In this systematic review, we summarized the preparation of nitrogen naphthoquinones derivatives and discussed their biological effect associated with redox properties and other mechanisms. Preclinical evaluation of antibacterial and/or antitumoral naphthoquinones derivatives is included because cancer is a worldwide health problem, and there is a lack of effective drugs against multidrug-resistant bacteria. The information presented herein indicates that naphthoquinone derivatives could be considered for further studies to provide drugs efficient in treating cancer and multidrug-resistant bacteria.

Pilot trial using mass field-releases of sterile males produced with the incompatible and sterile insect techniques as part of integrated Aedes aegypti control in Mexico.

BACKGROUND: The combination of Wolbachia-based incompatible insect technique (IIT) and radiation-based sterile insect technique (SIT) can be used for population suppression of Aedes aegypti. Our main objective was to evaluate whether open-field mass-releases of wAlbB-infected Ae. aegypti males, as part of an Integrated Vector Management (IVM) plan led by the Mexican Ministry of Health, could suppress natural populations of Ae. aegypti in urbanized settings in south Mexico. METHODOLOGY/PRINCIPAL FINDINGS: We implemented a controlled before-and-after quasi-experimental study in two suburban localities of Yucatan (Mexico): San Pedro Chimay (SPC), which received IIT-SIT, and San Antonio Tahdzibichén used as control. Release of wAlbB Ae. aegypti males at SPC extended for 6 months (July-December 2019), covering the period of higher Ae. aegypti abundance. Entomological indicators included egg hatching rates and outdoor/indoor adult females collected at the release and control sites. Approximately 1,270,000 lab-produced wAlbB-infected Ae. aegypti males were released in the 50-ha treatment area (2,000 wAlbB Ae. aegypti males per hectare twice a week in two different release days, totaling 200,000 male mosquitoes per week). The efficacy of IIT-SIT in suppressing indoor female Ae. aegypti density (quantified from a generalized linear mixed model showing a statistically significant reduction in treatment versus control areas) was 90.9% a month after initiation of the suppression phase, 47.7% two months after (when number of released males was reduced in 50% to match local abundance), 61.4% four months after (when initial number of released males was re-established), 88.4% five months after and 89.4% at six months after the initiation of the suppression phase. A proportional, but lower, reduction in outdoor female Ae. aegypti was also quantified (range, 50.0-75.2% suppression). CONCLUSIONS/SIGNIFICANCE: Our study, the first open-field pilot implementation of Wolbachia IIT-SIT in Mexico and Latin-America, confirms that inundative male releases can significantly reduce natural populations of Ae. aegypti. More importantly, we present successful pilot results of the integration of Wolbachia IIT-SIT within a IVM plan implemented by Ministry of Health personnel.

Wolbachia in Native Populations of Aedes albopictus (Diptera: Culicidae) From Yucatan Peninsula, Mexico.

This study reports the results of a molecular screening for Wolbachia (Wb) infection in Aedes albopictus (Skuse) populations recently established in the Yucatan Peninsula, Mexico. To do so, collections of free-flying adults with BG traps and emerged adults from eggs after ovitrap field collections were performed in three suburban localities of the city of Merida, Yucatan. Overall, local populations of Ae. albopictus present a natural Wb infection rate of ~40% (18 of 45). Wb infection was detected in both field-collected adults (76.5%, 13 of 17) and eggs reared (17.8%, 5 of 28) and in 37.9% (11/29) of females and 43.7% (7/16) of male Ae. albopictus mosquitoes. An initial screening for Wolbachia strain typing showed that native Ae. albopictus were naturally coinfected with both wAlbA and wAlbB strains. The knowledge of the prevalence and diversity of Wolbachia strains in local populations of Aedes mosquitoes is part of the baseline information required for current and future Wolbachia-based vector control approaches to be conducted in Mexico.

Disentangling Trypanosoma cruzi transmission cycle dynamics through the identification of blood meal sources of natural populations of Triatoma dimidiata in Yucatán, Mexico.

BACKGROUND: In the Yucatán Peninsula, Mexico, Triatoma dimidiata is the main vector of Trypanosoma cruzi, the causative agent of Chagas disease. Little effort has been made to identify blood meal sources of T. dimidiata in natural conditions in this region, although this provides key information to disentangle T. cruzi transmission cycles and dynamics and guide the development of more effective control strategies. We identified the blood meals of a large sample of T. dimidiata bugs collected in different ecotopes simultaneously with the assessment of bug infection with T. cruzi, to disentangle the dynamics of T. cruzi transmission in the region. METHODS: A sample of 248 T. dimidiata bugs collected in three rural villages and in the sylvatic habitat surrounding these villages was used. DNA from each bug midgut was extracted and bug infection with T. cruzi was assessed by PCR. For blood meal identification, we used a molecular assay based on cloning and sequencing following PCR amplification with vertebrate universal primers, and allowing the detection of multiple blood meals in a single bug. RESULTS: Overall, 28.7% of the bugs were infected with T. cruzi, with no statistical difference between bugs from the villages or from sylvatic ecotopes. Sixteen vertebrate species including domestic, synanthropic and sylvatic animals, were identified as blood meal sources for T. dimidiata. Human, dog and cow were the three main species identified, in bugs collected in the villages as well as in sylvatic ecotopes. Importantly, dog was highlighted as the main blood meal source after human. Dog was also the most frequently identified animal together with human within single bugs, and tended to be associated with the infection of the bugs. CONCLUSIONS: Dog, human and cow were identified as the main mammals involved in the connection of sylvatic and domestic transmission cycles in the Yucatán Peninsula, Mexico. Dog appeared as the most important animal in the transmission pathway of T. cruzi to humans, but other domestic and synanthropic animals, which most were previously reported as important hosts of T. cruzi in the region, were evidenced and should be taken into account as part of integrated control strategies aimed at disrupting parasite transmission.

Non-randomized controlled trial of the long-term efficacy of an Ecohealth intervention against Chagas disease in Yucatan, Mexico.

Non-domiciliated intrusive triatomine vectors are responsible for a low but significant transmission of Trypanosoma cruzi to humans. Their control is a challenge as insecticide spraying is of limited usefulness, and alternative strategies need to be developed for a sustainable control. We performed a non-randomized controlled trial of an Ecohealth intervention based on window insect screens and community participation to reduce house infestation by Triatoma dimidiata in two rural villages in Yucatan, Mexico. Efficacy of the intervention was measured over a three years follow-up period and entomological indicators showed that the proportion of triatomines found inside houses was significantly reduced in houses with insect screens, which effectively kept more bugs on the outside of houses. Using a previously developed model linking entomological data to the prevalence of infection in human, we predicted that the intervention would lead to a 32% reduction in yearly incidence and in the prevalence of T. cruzi infection. The cost for the coverage of all the windows of a house was of comparable magnitude to what families currently spend on various domestic insecticide, and most screens were still in good conditions after three years. In conclusion, the Ecohealth approach proposed here is effective for the long-term and sustainable control of intrusive T. dimidiata vectors in the Yucatan peninsula, Mexico. This strategy may also be easily adapted to other intrusive triatomine species as well as other regions/countries with comparable eco-epidemiological settings, and would be an excellent component of a larger integrated program for the control of a variety of other vector-borne diseases, bringing additional benefits to the communities. Our results should encourage a further scaling-up of our implementation strategy in additional villages in the region.

Detailed ecological associations of triatomines revealed by metabarcoding and next-generation sequencing: implications for triatomine behavior and Trypanosoma cruzi transmission cycles.

Trypanosoma cruzi is the agent of Chagas disease, transmitted by hematophagous triatomine vectors. Establishing transmission cycles is key to understand the epidemiology of the disease, but integrative assessments of ecological interactions shaping parasite transmission are still limited. Current approaches also lack sensitivity to assess the full extent of this ecological diversity. Here we developed a metabarcoding approach based on next-generation sequencing to identify triatomine gut microbiome, vertebrate feeding hosts, and parasite diversity and their potential interactions. We detected a dynamic microbiome in Triatoma dimidiata, including 23 bacterial orders, which differed according to blood sources. Fourteen vertebrate species served as blood sources, corresponding to domestic, synantropic and sylvatic species, although four (human, dog, cow and mice) accounted for over 50% of blood sources. Importantly, bugs fed on multiple hosts, with up to 11 hosts identified per bug, indicating very frequent host-switching. A high clonal diversity of T. cruzi was detected, with up to 20 haplotypes per bug. This analysis provided much greater sensitivity to detect multiple blood meals and multiclonal infections with T. cruzi, which should be taken into account to develop transmission networks, and characterize the risk for human infection, eventually leading to a better control of disease transmission.

Ultrasound-assisted reaction of 1,4-naphthoquinone with anilines through an EDA complex.

Naphthoquinone amino derivatives exhibit interesting physicochemical properties and a wide range of biological activities with potential medicinal applications. A clean, fast and simple method for the preparation of phenylamino-1,4-naphthoquinones is presented by the reaction of naphthoquinone (NQ) and anilines under ultrasound irradiation (US). Anilino derivatives were synthesized in good yields and shorter reaction times in comparison with the conventional method. This ultrasound procedure can be applied to the preparation of naphthoquinone derivatives with anilines containing electron-donor substituents (2-OMe, 4-OMe, 4-Me and 4-OEt) or halogen or electron-withdrawing substituents (4-F, 4-Cl, 4-Br, 3-F, 3-Cl, 3-Br, 4-Ac). This procedure was also applied to the reaction of anilines with 2,3-dichloro-1,4-naphthoquinone (DCNQ). A reaction mechanism involving an EDA complex is proposed based on NMR experiments and previous studies about solid/solid reactions.

Composición química de harina de calamar gigante dosidicus gigas / Chemical composition of giant squid dosidicus gigas meal

El potencial de uso de la harina de calamar gigante (Dosidicus gigas) (HCG). como alternativa en el desarrollo de productos con valor agregado es relevante. Sin embargo hace falta conocer los elementos químicos que la conforman. El objetivo de este trabajo fue determinar la composición química de la harina de calamar gigante (Dosidicus gigas) procedente de Guaymas, Sonora, México y su posible alternativa para el desarrollo de alimentos funcionales. Los resultados indicaron un alto contenido de proteína (77,7%), sobresaliendo lisina y ácido glutámico (10,16 y 14,53 g aa/100g proteína respectivamente), aminoácidos azufrados y aminoácidos hidrofóbicos. El contenido de la fracción grasa (6,3%) fue bajo así como el de fibra cruda (2,7%), reportada como quitina, reflejándose en el bajo aporte calórico (4 kcal/g). La relación entre ácidos grasos saturados, monoinsaturados y poliinsaturados fue de 1,66:1:1,08 y de n6:n3 fue de 1:1,35. Se concluye que HCG es un ingrediente con posibilidades de uso en panificación, galletas saladas, sazonadores, aderezos, a los que les podría dar un valor agregado. Sin embargo el factor limitante para su uso está en el olor y sabor a pescado, por lo que su aplicación se sugiere dirigir la aplicación hacia el desarrollo de nuevos productos vinculados con preparaciones típicas que incluyan pescados y derivados(AU)

The potential use of giant squid (Dosidicus gigas) meal (GSM) as an alternative in the development of value-added foods may be relevant. However one must know the chemical elements that constitute it. The aim of this study was to determine the chemical composition of giant squid Dosidicus gigas meal from Guaymas, Sonora, Mexico and its possible alternative for the development of functional foods. The data indicated a high protein content (77,7%), lysine and glutamic acid (10,16 and 14,53 g aa/100g protein respectively), sulfur amino acids and hydrophobic amino acids. The content of fat fraction (6,3%) was low and crude fiber (2,7%) reported as chitin, reflected in the low calorie (4 kcal/g). The ratio of saturated, monounsaturated and polyunsaturated fatty acids was 1,66: 1: 1,08 and n6: n3 was 1: 1,35. It is concluded that GSM is an ingredient with potential for use in bread, crackers, seasonings, dressings, which could give them added value. However the limiting factor for use is in the smell and taste of fish, so that its application would be directed at the development of new products related with typical preparations that include fish and derivatives(AU)

The marine algae Sargassum spp. (Sargassaceae) as feed for sheep in tropical and subtropical regions

The objective of this study was to evaluate Sargassum meal as feed for sheep through the measures of in vivo digestibility, dry matter degradability, pH, ammonia and volatile fatty acids in rumen. The Sargassum algae used in this experiment were collected at the end of spring, when they are more abundant, bigger, and have completed their reproductive cycle. Four tons (wet weigth) were collected manually from the intertidal zone of La Paz bay, Baja California Sur, Mexico. These algae were sun-dried and ground in a hammer mill to obtain the Sargassum meal. Four fistulated Pelibuey sheep, were fed daily with diets containing the marine algae (MA) at different levels (0, 10, 20 and 30 %), using a 4 x 4 Latin-square design experiment. Feed intake was not affected (p>0.05). Water consumption and urine excretion increased with MA (p<0.05; r²=0.54 and r²=0.74, respectively). In all treatments dry matter digestibility was of 74%-79%, and crude protein digestibility was of 85%-88%. Acid detergent fiber (59%-65%) and neutral detergent fiber (55%-66%) digestibility were greater in all treatments with MA. Ruminal pH was greater in all groups fed with MA (p<0.05). Ammonium concentration was not influenced (p>0.05) by MA. Ruminal volatile fatty acids decreased in all MA groups (p<0.05). The marine algae Sargassum spp. can be used as a feed supplement for sheep, especially in tropical and subtropical regions where these marine algae are available. Rev. Biol. Trop. 57 (4): 1271-1281. Epub 2009 December 01.

El objetivo de este estudio fue evaluar la harina del alga marina Sargassum como alimento para ovejas, midiendo la digestibilidad in vivo, la degradabilidad de la materia seca, así como el pH y los ácidos grasos volátiles en rumen. El alga Sargassum utilizada en este experimento, fue recolectada a finales de la primavera, cuando esta alga es más abundante, alcanza su mayor talla y ha completado su ciclo reproductivo. Se recolectaron manualmente, cuatro toneladas (peso húmedo) de la zona intermareal en la Bahía de La Paz, Baja California Sur, México. Estas algas fueron secadas directamente al sol y molidas en un molino de martillos, para obtener la harina. Se utilizaron cuatro borregos Pelibuey fistulados, distribuidos en un arreglo factorial de 4 x 4. Los animales fueron alimentados diariamente con dietas que contenían el alga marina (AM) Sargassum a diferentes niveles (0, 10, 20 y 30%). El consumo de alimento no se vio afectado con la inclusión del alga (p> 0.05). El consumo de agua y la excreción de orina se incrementaron conforme aumentó la concentración de AM en las dietas (p<0.05; r²=0.54 and r²=0.74, respectivamente). En todos los tratamientos la digestibilidad de la materia seca fue de 74% a 79%, la digestibilidad de la proteína cruda fue de 85% a 88%. La digestibilidad de la fibra ácido detergente (59%-65%) y de la neutro detergente (55%-66%) fue mayor en todos los tratamientos con AM, lo mismo ocurrió con el pH en rumen (p<0.05). La concentración de amonio en rumen no se vio afectada por AM (p>0.05). La concentración de ácidos grasos volátiles se redujo en todos los tratamientos con AM (p<0.05). El alga marina Sargassum spp. puede ser usada como complemento alimenticio para ovejas, especialmente en las regiones tropicales y subtropicales donde está disponible.

The marine algae Sargassum spp. (Sargassaceae) as feed for sheep in tropical and subtropical regions.

The objective of this study was to evaluate Sargassum meal as feed for sheep through the measures of in vivo digestibility, dry matter degradability, pH, ammonia and volatile fatty acids in rumen. The Sargassum algae used in this experiment were collected at the end of spring, when they are more abundant, bigger, and have completed their reproductive cycle. Four tons (wet weigth) were collected manually from the intertidal zone of La Paz bay, Baja California Sur, Mexico. These algae were sun-dried and ground in a hammer mill to obtain the Sargassum meal. Four fistulated Pelibuey sheep, were fed daily with diets containing the marine algae (MA) at different levels (0, 10, 20 and 30 %), using a 4 x 4 Latin-square design experiment. Feed intake was not affected (p>0.05). Water consumption and urine excretion increased with MA (p<0.05; r2=0.54 and r2=0.74, respectively). In all treatments dry matter digestibility was of 74%-79%, and crude protein digestibility was of 85%-88%. Acid detergent fiber (59%-65%) and neutral detergent fiber (55%-66%) digestibility were greater in all treatments with MA. Ruminal pH was greater in all groups fed with MA (p<0.05). Ammonium concentration was not influenced (p>0.05) by MA. Ruminal volatile fatty acids decreased in all MA groups (p<0.05). The marine algae Sargassum spp. can be used as a feed supplement for sheep, especially in tropical and subtropical regions where these marine algae are available.

Effect of sex hormones on non-esterified fatty acids, intra-abdominal fat accumulation, and hypertension induced by sucrose diet in male rats.

Sucrose-fed rats (1) had higher intra-abdominal fat mass and plasma non-esterified fatty acids and lower testosterone levels, (2) were hypertensive, and (3) had lower plasma NO metabolites than controls. The lack of testosterone by castration of sucrose-fed rats decreased high blood pressure and circulating non-esterified fatty acids and increased NO metabolites. The administration of testosterone to castrated sucrose-fed rats restored hypertension, fat accumulation, and high-circulating non-esterified fatty acids, and lowered NO metabolite levels whereas estradiol treatment did not significantly affect these variables in castrated animals. This study proposes that the low levels of testosterone found in sucrose-fed rats are sufficient to maintain central obesity and increased circulating non-esterified fatty acids, which contribute to the development of hypertension in sucrose-fed rats by modulating the biosynthesis of NO.

Generación de factores quimiotácticos para macrófagos alveolares, después de la instilación con asbesto crisotilo / Generation of chemotactic factors for alveolar macrophages after chrysotile asbestos instillation

Los modelos experimentales de asbestosis han demostrado que la respuesta inflamatoria inicial está mediada por macrófagos alveolares (MA). Aunque la atracción y acumulación de MA vistos en nuestros modelos está fundamentalmente mediada por el complemento, se ha sugerido la participación de otros factores quimiotácticos no bien caracterizados. En este trabajo, buscamos la presencia de factores quimiotácticos en ratas instiladas con asbesto en forma aguda. Demostramos morfoñlógicamente que el depósito de fibras, la respuesta macrofágica y las lesiones inducidas, son equivalentes a lo reportado en modelos por inhalación. Evaluamos la actividad quimiotáctica en el lavado broncoalveolar (LBA) fraccionado de acuerdo a su peso molecular (PM), y la presencia de albúmina y complemento. Encontramos actividad quimiotáctica en las fracciones del LBA correspondientes a picos de alto y bajo PM. La actividad del primer pico se atribuyó al complemento. La actividad del segundo, aumentó conforme al tiempo de exposición y no parece estar relacionada con complemento. Para identificar otros factores quimiotácticos diferentesa complemento, determinamos la presencia de factor de necrosis tumoral (TNFÿ) y fibronectina (FN) en los LBA no fraccionados. No se detectaron diferencias en la cantidad de TNF presente en los diferentes grupos. Observamos un incremento en la concentración de FN en relación al tiempo de exposición. Aunque la presencia de fracciones de FN pudiera explicar parcialmente el fenómeno quimiotáctico observado con el pico de bajo úPM, no podemos descartar la participación de otros factores no identificados