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  • Open access
  • 71 Reads
Generating optimal features to find out potent molecules against dengue virus: pharmacophore and QSAR approaches

Dengue is a threat of almost half of the population of most tropical and sub-tropical regions, mainly in Southeast Asia, the Pacific and the Americas, where the mosquito vectors, Aedes aegypti and Aedes albopictusare are profuse. Dengue fever is mainly caused by four major serotype of dengue virus i.e. DENV 1 to 4, but in 2013 a new serotype DENV-5 has been isolated. According to WHO, the first dengue vaccine, Dengvaxia® (CYD-TDV) developed by Sanofi Pasteur was licensed in December 2015 which is active against DENV1-4, but analysis showed that volunteers who were inferred to be seronegative at time of first vaccination had a higher risk of more severe dengue compared to unvaccinated volunteers. So, there are some disadvantages of using vaccine and no other treatments are available till now for dengue fever. The major drawback for dengue drug discovery is the lack of good small animal models, therefore we need computational or in-silico models with speed and accuracy which can facilitate dengue drug discovery. New approaches like Pharmacophore modelling and Quantitative Structure Activity Relationship (QSAR) can produce some valuable data which would be helpful for the designing of new chemical compounds as anti-dengue viral drug(s). Few evaluations of natural products as well as synthesised chemicals against different proteins of DENV have been published. In this present study, I have collated the entire molecule tested against DENV, and generating common ligand based pharmacophoric features from them, which could be helpful for the de novo synthesis and screening of compounds from databases against DENV. In addition, I am trying to develop 2D-QSAR models (using both congeneric series like different derivatives of α-ketoamides as well as non-congeneric series of molecules who’s biological activities are reported) to get some easily interpretable descriptors responsible for the activity. Finally, the generated hits will be undergoing for ADME analysis to investigate their drug-likeness properties followed by molecular docking and MD simulation to see their affinity against different proteins of DENV.

  • Open access
  • 186 Reads
Generating optimal features to find out potent molecules against dengue virus: pharmacophore and QSAR approaches

Dengue is a threat of almost half of the population of most tropical and sub-tropical regions, mainly in Southeast Asia, the Pacific and the Americas, where the mosquito vectors, Aedes aegypti and Aedes albopictusare are profuse. Dengue fever is mainly caused by four major serotype of dengue virus i.e. DENV 1 to 4, but in 2013 a new serotype DENV-5 has been isolated. According to WHO, the first dengue vaccine, Dengvaxia® (CYD-TDV) developed by Sanofi Pasteur was licensed in December 2015 which is active against DENV1-4, but analysis showed that volunteers who were inferred to be seronegative at time of first vaccination had a higher risk of more severe dengue compared to unvaccinated volunteers. So, there are some disadvantages of using vaccine and no other treatments are available till now for dengue fever. The major drawback for dengue drug discovery is the lack of good small animal models, therefore we need computational or in-silico models with speed and accuracy which can facilitate dengue drug discovery. New approaches like Pharmacophore modelling and Quantitative Structure Activity Relationship (QSAR) can produce some valuable data which would be helpful for the designing of new chemical compounds as anti-dengue viral drug(s). Few evaluations of natural products as well as synthesised chemicals against different proteins of DENV have been published. In this present study, I have collated the entire molecule tested against DENV, and generating common ligand based pharmacophoric features from them, which could be helpful for the de novo synthesis and screening of compounds from databases against DENV. In addition, I am trying to develop 2D-QSAR models (using both congeneric series like different derivatives of α-ketoamides as well as non-congeneric series of molecules who’s biological activities are reported) to get some easily interpretable descriptors responsible for the activity. Finally, the generated hits will be undergoing for ADME analysis to investigate their drug-likeness properties followed by molecular docking and MD simulation to see their affinity against different proteins of DENV.

  • Open access
  • 153 Reads
Web Application for Real Time Data Visualization of Heat Sensor

Calorimetry [1-5] and real-time monitoring systems [2,6-9], are essential aspects in environmental and agroindustrial processes. In this work, we develop a web application [6] that allows to remotely visualize continuous graphs of data coming from heat sensors connected to an Arduino device [10] with Internet access. The information is initially stored in a MySQL database [11-13], which reactively [14,15] generate the graph and the calculation of descriptive statistics [2,6-9].

  • Open access
  • 132 Reads
From In Vitro to In Cellulo: Evaluation of Anti-TNFα Activity of a New Series of Small Molecules

The Tumor Necrosis Factor alpha (TNFa) is a relevant clinical target for the treatment of chronic inflammatory diseases as rheumatoid arthritis or Crohn’s disease. Anti-TNFa biotherapies are used for the treatment of these diseases. They considerably improve patient living conditions but they are not without drawbacks. They cause side effects like accrue risk of infection, some patient develop resistance to these biotherapies and they are expensive. Small molecules inhibitors of TNFa would present fewer disadvantages than existing biotherapies, less side effects, no resistance, oral administration and would probably lead to less expensive treatments. Today only few small molecules are known as direct inhibitors of TNFa, SPD304 was the first small molecule described by He et al in 2005. None of these molecules showed both an efficient activity and a low toxicity, necessary to yield them into clinical trial.

The Laboratory GBA of Cnam has set-up a program aiming at finding new small molecules inhibitors of TNFa. A preview in silico docking study led to the identification of potential anti-TNFa molecules. Based on the docking results, new small molecules have been designed, synthetized and biologically evaluated.

Herein we describe the biological evaluation of a series of thirty new synthetized compounds for their capacity to inhibit the TNFa. These molecules were evaluated in vitro using two different immuno-assays (binding and shifting) and cell tests on two different cell lines.

  • Open access
  • 192 Reads
Study of acute toxicity of an aqueous abstract obtained from the flowers of Kigelia africana in Balb/c mice

Kigelia africana is used in traditional medicine and toxicological effects of the different extracts of the fruit, bark of the stem and leaf but not of its flowers have been reported, so the present investigation aims to determine the toxic potential of the aqueous extract obtained from the flowers of Kigelia africana by the acute toxic class method in Balb/c mice. An aqueous extract of the flowers was obtained, which was administered orally at a single dose of 50, 500 and 2000 mg/Kg and three Balb/c mice of different sexes were used in each level. With the administration of 50 and 500 mg/Kg doses, 100% survival was obtained, the daily systematic observations, the macroscopic analysis of the organs and their body weight showed no evidence of any sign of toxicity unlike the doses of 2000 mg/Kg where the deaths were observed in 48 hours being the main clinical symptoms depression of the central nervous system and polyuria marked with signs and symptoms of dehydration. The product can be classified in category 4.

  • Open access
  • 82 Reads
Evaluation of the noise pollution of the Cevallos avenue, Ambato city, Ecuador, for the determination of critical points of affectation in the place, and to provide information that allows the generation of preventive and corrective measures to the problem

In Latin American cities, economic activities generate environmental contamination directly or indirectly, one of the most important being noise pollution. The present study focuses on evaluating the environmental noise of Cevallos Avenue in Ambato City, taking into account that this location presents the most congestion of the city, both vehicular and pedestrian, and is one of the most important, due to the commercial activities and entertainment. Ambato is the tenth most populous city in Ecuador, with 175,000 inhabitants, and is located in the center of the inter-Andean region. Monitoring of the sound pressure level at four critical points of affectation (PCA) of the avenue was carried out, where measurements of noise emitting sources (FER), fixed and mobile, were made. This was carried out through four samplings at each point, spread over two days, and lasting for fifteen minutes each, following the methodology presented in Annex 5 of Book VI of the Unified Text of Secondary Legislation of the Ministry of the Environment (TULSMA, for its acronym in Spanish), regulations applied in Ecuador. The sound level meter used was CESVA brand, model SC310, with year of calibration 2017. To perform the measurements, this equipment was placed on a tripod located at a height equal to or higher than 1.5 m from the ground, thus placing the microphone towards the sound source with an inclination of 45 to 90 degrees, on the horizontal plane. The resulting values were compared with other works carried out in the study area, and it was determined that 95% does not comply with the maximum permissible limits presented in the current Ecuadorian environmental regulations, both in day and night periods.

  • Open access
  • 94 Reads
SCREEING OF HYDRO-ALCOHOLIC EXTRACT OF FRUITS OF LUFFA CYLINDRICA LINN. ON ASPIRIN PLUS PYLORUS LIGATED RAT MODEL: FOR ITS ANTI-ULCER ACTIVITY

The traditional systems of treatment such as Ayurveda, Unani, and Siddha, western herbal medicine, traditional Chinese medicine and homeopathy use herbs for the treatment. Many researchers has prescribed about the importance of herbal medicine in the treatment of various diseases and because of the accessibility and cost effectiveness herbal treatment is still in practice by large number of practitioners. Luffa cylindrica Linn. (Curcubitaceace ) fruits was reported to possess a number of medicinal properties including used as immunostimulant, anti-inflammatory, anti-tumour, antibacterial, antifungal and anti-viral activities and also induce uterine contraction to hasten child birth (Oxytocics). The present study was investigated the anti-ulcer activity of hydroalcoholic extracts of fruits of luffa cylindrica Linn by using aspirin plus pylorus ligated model at the dose of 100 and 200 mg/kg. The results were showed significantly (p<0.01) decreased in ulcer index (1.31±0.33) and gastric volume (2.18±0.74) when compared with control (3.92±0.27) and 95.85±0.12) respectively at the dose of 200 m/kg and also showed significant effect when compared with omeprazole (standard) at 2mg/kg. In this study concluded that the hydroalcoholic extract of fruit of luffa cylindrica act as anti-ulcer activity due to presence of alkaloids and flavonoids.

  • Open access
  • 95 Reads
Isolation of Erwinia amylovora Bacteriophage from Soil and Pear Trees Plant Tissues

Attributed to a Gram-negative bacterium, identified as Erwinia amylovora, the fire blight disease, recently detected in Tunisia, has become a real threat to our economy and our arboriculture.
There is no effective curative treatment to eliminate the installed bacterium. It is therefore essential to prevent attacks and to limit the spread of the bacteria if it is already present. To do so we have chosen the biocontrol by bacteriophages.

In this work we have isolated new strains of Erwinia amylovora (10 strains) from plant tissues where fire blight symptoms are persistent. These strains have been the subject of a molecular study.

The isolated phages (30 isolates) were studied for their infectivity on Erwinia amylovora isolates and showed a surprising effect. Our phage isolates formed plaque of different sizes, with a diameter ranging between 0.5 and 2mm on the soft agar layer containing the test bacterium. The phages thermostability showed that all these viruses resist at 80 ° C for 45 min

  • Open access
  • 62 Reads
LIVER CANCER IN CHILDREN

LIVER CANCER IN CHILDREN- A REVIEW

  1. N.Charan Raj, Dr .ch .ananda kumar, Dr .D.mohanty , Dr. A.madhu babu and Dr . B.vasudha bakshi.

School of Pharmacy, Anurag Group of Institutions,(formerly cvsr college of engeneering)

Venkatapur,Ghatkesar,Medchal Dist-500038, Telangana.

It is unclear exactly what causes liver cancer, but researchers know that it develops due to mutations in liver cells. These cells grow without the usual regulation that tells liver cells when to replicate and when to stop replicating. When cells replicate without regulation, they can become a tumor. Some children are diagnosed with hepatoblastoma so young that scientists believe the cancer starts before the children are born. Hepatocellular Carcinoma is seen more frequently in areas of the world that have high rates of hepatitis. Infection with any one of several viruses that cause hepatitis is believed to be responsible. Only a few risk factors for hepatoblastoma are known for sure. Children with some genetic syndromes are more likely to develop hepatoblastoma than other children. Babies with low birth weights (less than 1,500 grams or about 3 1/2 pounds at birth) have a much higher risk of hepatoblastoma compared to normal weight babies. Smaller than average babies (3 pounds 5 ounces – 5 pounds 8 ounces) have a slightly increased risk of developing hepatoblastoma. The reasons for the high risk associated with lower birth weights are not clear. Most children who are born with low birth weight never develop hepatoblastoma. HCC is more common in males compared to females. Hepatitis B virus passed from mother at childbirth is a HCC risk factor. Other risk factors for HCC include inherited metabolic disorders such as hereditary tyrosinemia, alpha-1-antitrypsin deficiency, disorders that lead to bile accumulation in the liver (such as Alagille syndrome) and glycogen storage disease. Obesity, hereditary hemochromatosis (too much iron accumulation in the body) and Wilson’s disease (too much copper accumulation) can also lead to liver damage and HCC.

  • Open access
  • 182 Reads
A new simplex machine learning approach for analysis of structural chemical diversification processes. Comparison with other molecular modeling methods.

Metabolism represents highly organized system characterized by strong regulations satisfying the mass conservation principle. In this work, a new simplex-based simulation approach was developed to learn scaffold information on metabolic processes controlling molecular diversity from a wide set of observed chemical structures. This approach is based on iterative in silico combinations of molecular profiles using Scheffé’s mixture design. It was illustrated by cycloartane-based saponins of Astragalus genus containing one, two or three ramification chains with variable relative glycosylation levels. Comparisons between this simplex approach and other molecular modeling approaches were made to highlight advantages and limits of the new one.

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