Bioprospecting Antiproliferative Marine Microbiota From Submarine Volcano Tagoro

Marine ecosystems are unique and rich reservoirs of biodiversity with high potential toward improving the quality of human life. The extreme physical–chemical conditions of the oceans have favored marine organisms to produce a great variety of new molecules as a mechanism to ensure their survival, and such compounds possess great biopharmaceutical interest. In particular, marine microbiota represent a promising and inexhaustible source for the development of new drugs. This work presents the taxonomic study of the samples obtained from the underwater volcano Tagoro, which has allowed us to develop a collection of 182 marine bacterial strains. On October 10th, 2011, at La Restinga–El Mar de Las Calmas Marine Reserve, an underwater eruption gave rise to a novel shallow submarine volcano at 1.8 km south of the island of El Hierro, Canary Islands, Spain. During the first 6 months, extreme physical–chemical perturbations, comprising thermal changes, water acidification, deoxygenation, and metal enrichment, resulted in significant alterations of the marine ecosystem. After March 2012, the submarine volcano Tagoro entered an active hydrothermal phase that involved a release of heat, gases, metals, and micronutrients that continues till our present. During 2016, our research team had the opportunity to participate in one of the monitoring oceanographic cruises carried out in the area in order to isolate microorganisms associated with both rock samples and deep-sea invertebrates over Tagoro submarine volcano. In this study, Proteobacteria revealed as the most abundant Phylum with 70.2% among all isolated strains, followed by Firmicutes 19%, Actinobacteria 9.5%, and Bacteroidetes 1.2%. Furthermore, we present the results of the antiproliferative assays of the extracts obtained from small-scale cultures of selected bacterial strains. An analysis of the effects of culture conditions in the antiproliferative activity showed that strains grown in Marine Broth (MB) presented lower GI50 values than those cultured in a modified medium (MM1). This effect is improved when the strains are incubated under agitation conditions. The antiproliferative potential of genera such as Halobacillus, Kangiella, Photobacterium, and Halomonas is revealed. Their biotechnological development provides an excellent starting point to access novel secondary metabolites and enzymes with potential for pharmaceutical and industrial applications.

Download Full-text

Benzimidazole Derivatives as New and Selective Inhibitors of Arginase from Leishmania mexicana with Biological Activity against Promastigotes and Amastigotes

International Journal of Molecular Sciences ◽

10.3390/ijms222413613 ◽

2021 ◽

Vol 22 (24) ◽

pp. 13613

Author(s):

Irene Betancourt-Conde ◽

Claudia Avitia-Domínguez ◽

Alicia Hernández-Campos ◽

Rafael Castillo ◽

Lilián Yépez-Mulia ◽

...

Keyword(s):

Biological Activity ◽

In Silico ◽

Cytotoxic Effect ◽

New Drugs ◽

Dynamics Simulation ◽

Benzimidazole Derivatives ◽

Leishmania Mexicana ◽

Arginase 1 ◽

Excellent Starting Point ◽

Starting Point

Leishmaniasis is a disease caused by parasites of the Leishmania genus that affects 98 countries worldwide, 2 million of new cases occur each year and more than 350 million people are at risk. The use of the actual treatments is limited due to toxicity concerns and the apparition of resistance strains. Therefore, there is an urgent necessity to find new drugs for the treatment of this disease. In this context, enzymes from the polyamine biosynthesis pathway, such as arginase, have been considered a good target. In the present work, a chemical library of benzimidazole derivatives was studied performing computational, enzyme kinetics, biological activity, and cytotoxic effect characterization, as well as in silico ADME-Tox predictions, to find new inhibitors for arginase from Leishmania mexicana (LmARG). The results show that the two most potent inhibitors (compounds 1 and 2) have an I50 values of 52 μM and 82 μM, respectively. Moreover, assays with human arginase 1 (HsARG) show that both compounds are selective for LmARG. According to molecular dynamics simulation studies these inhibitors interact with important residues for enzyme catalysis. Biological activity assays demonstrate that both compounds have activity against promastigote and amastigote, and low cytotoxic effect in murine macrophages. Finally, in silico prediction of their ADME-Tox properties suggest that these inhibitors support the characteristics to be considered drug candidates. Altogether, the results reported in our study suggest that the benzimidazole derivatives are an excellent starting point for design new drugs against leishmanisis.

Download Full-text

Two isoprenylated flavonoids from Dorstenia psilurus activate AMPK, stimulate glucose uptake, inhibit glucose production and lower glycemia

Biochemical Journal ◽

10.1042/bcj20190326 ◽

2019 ◽

Vol 476 (24) ◽

pp. 3687-3704 ◽

Cited By ~ 2

Author(s):

Aphrodite T. Choumessi ◽

Manuel Johanns ◽

Claire Beaufay ◽

Marie-France Herent ◽

Vincent Stroobant ◽

...

Keyword(s):

Glucose Uptake ◽

Human Cancer ◽

Glucose Production ◽

Liver Mitochondria ◽

New Drugs ◽

Structural Isomer ◽

Rat Liver Mitochondria ◽

Ionization Mass ◽

Ampk Activation ◽

Starting Point

Root extracts of a Cameroon medicinal plant, Dorstenia psilurus, were purified by screening for AMP-activated protein kinase (AMPK) activation in incubated mouse embryo fibroblasts (MEFs). Two isoprenylated flavones that activated AMPK were isolated. Compound 1 was identified as artelasticin by high-resolution electrospray ionization mass spectrometry and 2D-NMR while its structural isomer, compound 2, was isolated for the first time and differed only by the position of one double bond on one isoprenyl substituent. Treatment of MEFs with purified compound 1 or compound 2 led to rapid and robust AMPK activation at low micromolar concentrations and increased the intracellular AMP:ATP ratio. In oxygen consumption experiments on isolated rat liver mitochondria, compound 1 and compound 2 inhibited complex II of the electron transport chain and in freeze–thawed mitochondria succinate dehydrogenase was inhibited. In incubated rat skeletal muscles, both compounds activated AMPK and stimulated glucose uptake. Moreover, these effects were lost in muscles pre-incubated with AMPK inhibitor SBI-0206965, suggesting AMPK dependency. Incubation of mouse hepatocytes with compound 1 or compound 2 led to AMPK activation, but glucose production was decreased in hepatocytes from both wild-type and AMPKβ1−/− mice, suggesting that this effect was not AMPK-dependent. However, when administered intraperitoneally to high-fat diet-induced insulin-resistant mice, compound 1 and compound 2 had blood glucose-lowering effects. In addition, compound 1 and compound 2 reduced the viability of several human cancer cells in culture. The flavonoids we have identified could be a starting point for the development of new drugs to treat type 2 diabetes.

Download Full-text

Indirect Assessment of Attitudes with Response-Time-Based Measures

Zeitschrift für Sozialpsychologie ◽

10.1024/0044-3514.37.3.131 ◽

2006 ◽

Vol 37 (3) ◽

pp. 131-139 ◽

Cited By ~ 15

Author(s):

Juliane Degner ◽

Dirk Wentura ◽

Klaus Rothermund

Keyword(s):

Social Cognitive ◽

Incremental Validity ◽

Self Report ◽

Small Scale ◽

Implicit Measures ◽

Scale Theory ◽

Starting Point ◽

Self Reports ◽

Predicting Behavior ◽

Social Cognitive Theories

Abstract: We review research on response-latency based (“implicit”) measures of attitudes by examining what hopes and intentions researchers have associated with their usage. We identified the hopes of (1) gaining better measures of interindividual differences in attitudes as compared to self-report measures (quality hope); (2) better predicting behavior, or predicting other behaviors, as compared to self-reports (incremental validity hope); (3) linking social-cognitive theories more adequately to empirical research (theory-link hope). We argue that the third hope should be the starting point for using these measures. Any attempt to improve these measures should include the search for a small-scale theory that adequately explains the basic effects found with such a measure. To date, small-scale theories for different measures are not equally well developed.

Download Full-text

Small-scale vegetation mapping of large territories: perspectives of using modern remote sensing and GIS technologies, the Indian experiences

Geobotanical mapping ◽

10.31111/geobotmap/1994-1995.51 ◽

1996 ◽

pp. 51-54 ◽

Cited By ~ 1

Author(s):

N. V. M. Unni

Keyword(s):

Remote Sensing ◽

Satellite Remote Sensing ◽

Forest Cover ◽

Human Life ◽

Remote Sensing Data ◽

Modern World ◽

Small Scale ◽

Vegetation Map ◽

Gis Technologies ◽

Forest Cover Mapping

The recognition of versatile importance of vegetation for the human life resulted in the emergence of vegetation science and many its applications in the modern world. Hence a vegetation map should be versatile enough to provide the basis for these applications. Thus, a vegetation map should contain not only information on vegetation types and their derivatives but also the geospheric and climatic background. While the geospheric information could be obtained, mapped and generalized directly using satellite remote sensing, a computerized Geographic Information System can integrate it with meaningful vegetation information classes for large areas. Such aft approach was developed with respect to mapping forest vegetation in India at. 1 : 100 000 (1983) and is in progress now (forest cover mapping at 1 : 250 000). Several review works reporting the experimental and operational use of satellite remote sensing data in India were published in the last years (Unni, 1991, 1992, 1994).

Download Full-text

Chemometric Analysis for the Classification of some Groups of Drugs with Divergent Pharmacological Activity on the Basis of some Chromatographic and Molecular Modeling Parameters

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207321666180129102149 ◽

2018 ◽

Vol 21 (2) ◽

pp. 125-137

Author(s):

Jolanta Stasiak ◽

Marcin Koba ◽

Marcin Gackowski ◽

Tomasz Baczek

Keyword(s):

Correlation Analysis ◽

Pharmacological Activity ◽

Correlation Coefficients ◽

Principal Component ◽

Cardiovascular Drugs ◽

New Drugs ◽

Analgesic Drugs ◽

Starting Point ◽

Chromatographic Parameters

Aim and Objective: In this study, chemometric methods as correlation analysis, cluster analysis (CA), principal component analysis (PCA), and factor analysis (FA) have been used to reduce the number of chromatographic parameters (logk/logkw) and various (e.g., 0D, 1D, 2D, 3D) structural descriptors for three different groups of drugs, such as 12 analgesic drugs, 11 cardiovascular drugs and 36 “other” compounds and especially to choose the most important data of them. Material and Methods: All chemometric analyses have been carried out, graphically presented and also discussed for each group of drugs. At first, compounds’ structural and chromatographic parameters were correlated. The best results of correlation analysis were as follows: correlation coefficients like R = 0.93, R = 0.88, R = 0.91 for cardiac medications, analgesic drugs, and 36 “other” compounds, respectively. Next, part of molecular and HPLC experimental data from each group of drugs were submitted to FA/PCA and CA techniques. Results: Almost all results obtained by FA or PCA, and total data variance, from all analyzed parameters (experimental and calculated) were explained by first two/three factors: 84.28%, 76.38 %, 69.71% for cardiovascular drugs, for analgesic drugs and for 36 “other” compounds, respectively. Compounds clustering by CA method had similar characteristic as those obtained by FA/PCA. In our paper, statistical classification of mentioned drugs performed has been widely characterized and discussed in case of their molecular structure and pharmacological activity. Conclusion: Proposed QSAR strategy of reduced number of parameters could be useful starting point for further statistical analysis as well as support for designing new drugs and predicting their possible activity.

Download Full-text

Design of Inhibitors for Glyceraldehyde-3-phosphate Dehydrogenase (GAPDH) Enzyme of Leishmania mexicana

Medicinal Chemistry ◽

10.2174/1573406415666190712111139 ◽

2020 ◽

Vol 16 (6) ◽

pp. 784-795

Author(s):

Krisnna M.A. Alves ◽

Fábio José Bonfim Cardoso ◽

Kathia M. Honorio ◽

Fábio A. de Molfetta

Keyword(s):

Molecular Dynamics ◽

Molecular Dynamics Simulations ◽

Binding Site ◽

Point Of View ◽

New Drugs ◽

Leishmania Mexicana ◽

Receptor Complexes ◽

Starting Point ◽

Dynamics Simulations ◽

Selection Of

Background:: Leishmaniosis is a neglected tropical disease and glyceraldehyde 3- phosphate dehydrogenase (GAPDH) is a key enzyme in the design of new drugs to fight this disease. Objective:: The present study aimed to evaluate potential inhibitors of GAPDH enzyme found in Leishmania mexicana (L. mexicana). Methods: A search for novel antileishmanial molecules was carried out based on similarities from the pharmacophoric point of view related to the binding site of the crystallographic enzyme using the ZINCPharmer server. The molecules selected in this screening were subjected to molecular docking and molecular dynamics simulations. Results:: Consensual analysis of the docking energy values was performed, resulting in the selection of ten compounds. These ligand-receptor complexes were visually inspected in order to analyze the main interactions and subjected to toxicophoric evaluation, culminating in the selection of three compounds, which were subsequently submitted to molecular dynamics simulations. The docking results showed that the selected compounds interacted with GAPDH from L. mexicana, especially by hydrogen bonds with Cys166, Arg249, His194, Thr167, and Thr226. From the results obtained from molecular dynamics, it was observed that one of the loop regions, corresponding to the residues 195-222, can be related to the fitting of the substrate at the binding site, assisting in the positioning and the molecular recognition via residues responsible for the catalytic activity. Conclusion:: he use of molecular modeling techniques enabled the identification of promising compounds as inhibitors of the GAPDH enzyme from L. mexicana, and the results obtained here can serve as a starting point to design new and more effective compounds than those currently available.

Download Full-text

CYBERCHONDRIA INFORMATION CLINIC: Internet's Impact on your Health (Preprint)

10.2196/preprints.14507 ◽

2019 ◽

Author(s):

Valentina Escotet Espinoza

Keyword(s):

Human Life ◽

Brain Regions ◽

Physical Symptoms ◽

Digital Design ◽

Somatization Disorder ◽

The Internet ◽

Cultural Aspects ◽

Starting Point ◽

The Right ◽

The Relationship

UNSTRUCTURED Over half of Americans report looking up health-related questions on the internet, including questions regarding their own ailments. The internet, in its vastness of information, provides a platform for patients to understand how to seek help and understand their condition. In most cases, this search for knowledge serves as a starting point to gather evidence that leads to a doctor’s appointment. However, in some cases, the person looking for information ends up tangled in an information web that perpetuates anxiety and further searches, without leading to a doctor’s appointment. The Internet can provide helpful and useful information; however, it can also be a tool for self-misdiagnosis. Said person craves the instant gratification the Internet provides when ‘googling’ – something one does not receive when having to wait for a doctor’s appointment or test results. Nevertheless, the Internet gives that instant response we demand in those moments of desperation. Cyberchondria, a term that has entered the medical lexicon in the 21st century after the advent of the internet, refers to the unfounded escalation of people’s concerns about their symptomatology based on search results and literature online. ‘Cyberchondriacs’ experience mistrust of medical experts, compulsion, reassurance seeking, and excessiveness. Their excessive online research about health can also be associated with unnecessary medical expenses, which primarily arise from anxiety, increased psychological distress, and worry. This vicious cycle of searching information and trying to explain current ailments derives into a quest for associating symptoms to diseases and further experiencing the other symptoms of said disease. This psychiatric disorder, known as somatization, was first introduced to the DSM-III in the 1980s. Somatization is a psycho-biological disorder where physical symptoms occur without any palpable organic cause. It is a disorder that has been renamed, discounted, and misdiagnosed from the beginning of the DSMs. Somatization triggers span many mental, emotional, and cultural aspects of human life. Our environment and social experiences can lay the blueprint for disorders to develop over time; an idea that is widely accepted for underlying psychiatric disorders such as depression and anxiety. The research is going in the right direction by exploring brain regions but needs to be expanded on from a sociocultural perspective. In this work, we explore the relationship between somatization disorder and the condition known as cyberchondria. First, we provide a background on each of the disorders, including their history and psychological perspective. Second, we proceed to explain the relationship between the two disorders, followed by a discussion on how this relationship has been studied in the scientific literature. Thirdly, we explain the problem that the relationship between these two disorders creates in society. Lastly, we propose a set of intervention aids and helpful resource prototypes that aim at resolving the problem. The proposed solutions ranged from a site-specific clinic teaching about cyberchondria to a digital design-coded chrome extension available to the public.

Download Full-text

Improved synthesis of SV2A targeting radiotracer [11C]UCB-J

EJNMMI Radiopharmacy and Chemistry ◽

10.1186/s41181-019-0080-5 ◽

2019 ◽

Vol 4 (1) ◽

Cited By ~ 2

Author(s):

Johanna Rokka ◽

Eva Schlein ◽

Jonas Eriksson

Keyword(s):

Methyl Iodide ◽

Water Solution ◽

Synthesis Method ◽

Radiochemical Yield ◽

Preparative Hplc ◽

Step Method ◽

Synaptic Density ◽

Excellent Starting Point ◽

Starting Point

Abstract Introduction [11C]UCB-J is a tracer developed for PET (positron emission tomography) that has high affinity towards synaptic vesicle glycoprotein 2A (SV2A), a protein believed to participate in the regulation of neurotransmitter release in neurons and endocrine cells. The localisation of SV2A in the synaptic terminals makes it a viable target for in vivo imaging of synaptic density in the brain. Several SV2A targeting compounds have been evaluated as PET tracers, including [11C]UCB-J, with the aim to facilitate studies of synaptic density in neurological diseases. The original two-step synthesis method failed in our hands to produce sufficient amounts of [11C]UCB-J, but served as an excellent starting point for further optimizations towards a high yielding and simplified one-step method. [11C]Methyl iodide was trapped in a clear THF-water solution containing the trifluoroborate substituted precursor, potassium carbonate and palladium complex. The resulting reaction mixture was heated at 70 °C for 4 min to produce [11C]UCB-J. Results After semi-preparative HPLC purification and reformulation in 10% ethanol/phosphate buffered saline, the product was obtained in 39 ± 5% radiochemical yield based on [11C]methyl iodide, corresponding to 1.8 ± 0.5 GBq at EOS. The radiochemical purity was > 99% and the molar activity was 390 ± 180 GBq/μmol at EOS. The product solution contained < 2 ppb palladium. Conclusions A robust and high yielding production method has been developed for [11C]UCB-J, suitable for both preclinical and clinical PET applications.

Download Full-text

Globalization Impact on Multinational Enterprises

World ◽

10.3390/world2020014 ◽

2021 ◽

Vol 2 (2) ◽

pp. 216-230

Author(s):

Justine Kyove ◽

Katerina Streltsova ◽

Ufuoma Odibo ◽

Giuseppe T. Cirella

Keyword(s):

Developing Country ◽

Multinational Enterprises ◽

Developed Countries ◽

Global Market ◽

Data Availability ◽

Negative Effects ◽

Developed Country ◽

Excellent Starting Point ◽

Starting Point ◽

The Impact

The impact of globalization on multinational enterprises was examined from the years 1980 to 2020. A scoping literature review was conducted for a total of 141 articles. Qualitative, quantitative, and mixed typologies were categorized and conclusions were drawn regarding the influence and performance (i.e., positive or negative effects) of globalization. Developed countries show more saturated markets than developing countries that favor developing country multinational enterprises to rely heavily on foreign sales for revenue growth. Developed country multinationals are likely to use more advanced factors of production to create revenue, whereas developing country multinationals are more likely to use less advanced forms. A number of common trends and issues showed corporate social responsibility, emerging markets, political issues, and economic matters as key to global market production. Recommendations signal a strong need for more research that addresses contributive effects in the different economies, starting with the emerging to the developed. Limitations of data availability and inconsistency posed a challenge for this review, yet the use of operationalization, techniques, and analyses from the business literature enabled this study to be an excellent starting point for additional work in the field.

Download Full-text

Antimicrobial, Antioxidant, Anti-Acetylcholinesterase, Antidiabetic, and Pharmacokinetic Properties of Carum carvi L. and Coriandrum sativum L. Essential Oils Alone and in Combination

Molecules ◽

10.3390/molecules26123625 ◽

2021 ◽

Vol 26 (12) ◽

pp. 3625

Author(s):

Hafedh Hajlaoui ◽

Soumaya Arraouadi ◽

Emira Noumi ◽

Kaïss Aouadi ◽

Mohd Adnan ◽

...

Keyword(s):

Essential Oils ◽

Coriandrum Sativum ◽

New Drugs ◽

Antidiabetic Activity ◽

Pharmacokinetic Analysis ◽

Bacterial Strains ◽

Standard Drug ◽

Reference Drug ◽

Antioxidant Power ◽

Carum Carvi

Herbs and spices have been used since antiquity for their nutritional and health properties, as well as in traditional remedies for the prevention and treatment of many diseases. Therefore, this study aims to perform a chemical analysis of both essential oils (EOs) from the seeds of Carum carvi (C. carvi) and Coriandrum sativum (C. sativum) and evaluate their antioxidant, antimicrobial, anti-acetylcholinesterase, and antidiabetic activities alone and in combination. Results showed that the EOs mainly constitute monoterpenes with γ-terpinene (31.03%), β-pinene (18.77%), p-cymene (17.16%), and carvone (12.20%) being the major components present in C. carvi EO and linalool (76.41%), γ-terpinene (5.35%), and α-pinene (4.44%) in C. sativum EO. In comparison to standards, statistical analysis revealed that C. carvi EO showed high and significantly different (p < 0.05) antioxidant activity than C. sativum EO, but lower than the mixture. Moreover, the mixture exhibited two-times greater ferric ion reducing antioxidant power (FRAP) (IC50 = 11.33 ± 1.53 mg/mL) and equipotent chelating power (IC50 = 31.33 ± 0.47 mg/mL) than the corresponding references, and also potent activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) (IC50 = 19.00 ± 1.00 mg/mL), β-carotene (IC50 = 11.16 ± 0.84 mg/mL), and superoxide anion (IC50 = 10.33 ± 0.58 mg/mL) assays. Antimicrobial data revealed that single and mixture EOs were active against a panel of pathogenic microorganisms, and the mixture had the ability to kill more bacterial strains than each EO alone. Additionally, the anti-acetylcholinesterase and α-glucosidase inhibitory effect have been studied for the first time, highlighting the high inhibition effect of AChE by C. carvi (IC50 = 0.82 ± 0.05 mg/mL), and especially by C. sativum (IC50 = 0.68 ± 0.03 mg/mL), as well as the mixture (IC50 = 0.63 ± 0.02 mg/mL) compared to the reference drug, which are insignificantly different (p > 0.05). A high and equipotent antidiabetic activity was observed for the mixture (IC50 = 0.75 ± 0.15 mg/mL) when compared to the standard drug, acarbose, which is about nine times higher than each EO alone. Furthermore, pharmacokinetic analysis provides some useful insights into designing new drugs with favorable drug likeness and safety profiles based on a C. carvi and C. sativum EO mixture. In summary, the results of this study revealed that the combination of these EOs may be recommended for further food, therapeutic, and pharmaceutical applications, and can be utilized as medicine to inhibit several diseases.

Download Full-text