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https://www.readbyqxmd.com/read/30110923/current-screening-methodologies-in-drug-discovery-for-selected-human-diseases
#1
REVIEW
Olga Maria Lage, María C Ramos, Rita Calisto, Eduarda Almeida, Vitor Vasconcelos, Francisca Vicente
The increase of many deadly diseases like infections by multidrug-resistant bacteria implies re-inventing the wheel on drug discovery. A better comprehension of the metabolisms and regulation of diseases, the increase in knowledge based on the study of disease-born microorganisms' genomes, the development of more representative disease models and improvement of techniques, technologies, and computation applied to biology are advances that will foster drug discovery in upcoming years. In this paper, several aspects of current methodologies for drug discovery of antibacterial and antifungals, anti-tropical diseases, antibiofilm and antiquorum sensing, anticancer and neuroprotectors are considered...
August 14, 2018: Marine Drugs
https://www.readbyqxmd.com/read/30104527/chalcones-repressed-the-aurka-and-mdr-proteins-involved-in-metastasis-and-multiple-drug-resistance-in-breast-cancer-cell-lines
#2
Tatiana Takahasi Komoto, Tayná Minervina Bernardes, Thaís Balthazar Mesquita, Luis Felipe Buso Bortolotto, Gabriel Silva, Tamires Aparecida Bitencourt, Seung Joon Baek, Mozart Marins, Ana Lúcia Fachin
In the present investigation, trans -chalcone and licochalcone A were tested against MCF-7 and BT-20 breast cancer cell lines for anti-tumor activity. We found that both chalcones down regulated important genes associated to cancer development and inhibited cell migration of metastatic cells (BT-20). Finally, we observed that licochalcone A reduces the MDR-1 protein, while both chalcones suppress the AURKA protein in a dose-dependent manner. In conclusion, we observed the trans -chalcone and licochalcone A affected the cell viability of breast cancer cell lines MCF-7 and BT-20 and presents anti-metastatic and anti-resistance potential, by the repression of AUKA and MDR-1 proteins...
August 13, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/30087892/technoeconomic-modeling-of-plant-based-griffithsin-manufacturing
#3
Aatif Alam, Linda Jiang, Gregory A Kittleson, Kenneth D Steadman, Somen Nandi, Joshua L Fuqua, Kenneth E Palmer, Daniel Tusé, Karen A McDonald
Griffithsin is a marine algal lectin that exhibits broad-spectrum antiviral activity by binding oligomannose glycans on viral envelope glycoproteins, including those found in HIV-1, HSV-2, SARS, HCV and other enveloped viruses. An efficient, scalable and cost-effective manufacturing process for Griffithsin is essential for the adoption of this drug in human antiviral prophylaxis and therapy, particularly in cost-sensitive indications such as topical microbicides for HIV-1 prevention. The production of certain classes of recombinant biologics in plants can offer scalability, cost and environmental impact advantages over traditional biomanufacturing platforms...
2018: Frontiers in Bioengineering and Biotechnology
https://www.readbyqxmd.com/read/30087223/green-synthesis-of-gold-nanoparticles-using-carrageenan-oligosaccharide-and-their-in-vitro-antitumor-activity
#4
Xiangyan Chen, Xia Zhao, Yanyun Gao, Jiaqi Yin, Mingyue Bai, Fahe Wang
Gold nanoparticles (AuNPs) have been widely used in catalysis, photothermal therapy, and targeted drug delivery. Carrageenan oligosaccharide (CAO) derived from marine red algae was used as a reducing and capping agent to obtain AuNPs by an eco-friendly, efficient, and simple synthetic route for the first time. The synthetic conditions of AuNPs were optimized by response surface methodology (RSM), and the CAO-AuNPs obtained were demonstrated to be ellipsoidal, stable and crystalline by means of transmission electron microscopy (TEM), scanning electron microscopy (SEM) and X-ray diffraction (XRD)...
August 7, 2018: Marine Drugs
https://www.readbyqxmd.com/read/30083931/glycans-with-antiviral-activity-from-marine-organisms
#5
I D Grice, G L Mariottini
There remains today a critical need for new antiviral agents, particularly in view of the alarming increase in drug resistance and associated issues. The marine environment has been a prolific contributor towards the identification of novel therapeutic agents in the recent few decades. Added to this, glycans (or carbohydrate- or sugar-based compounds) have in very recent decades made outstanding contributions to the development of novel therapeutics. This review brings together these significant facets of modern drug discovery by presenting the reported literature on glycans derived from marine organisms that possess antiviral activity...
2018: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/30082294/trend-and-pattern-of-antimicrobial-resistance-in-molluscan-vibrio-species-sourced-to-canadian-estuaries
#6
Swapan K Banerjee, Jeffrey M Farber
Emergence of antimicrobial resistance (AMR) in foodborne bacteria is a growing concern worldwide. AMR surveillance is a key element in understanding the implications resulting from the use of antibiotics for therapeutic as well as prophylactic needs. The emergence and spread of AMR in foodborne human pathogens is an indirect health hazard. This surveillance study reports the trend and pattern of AMR detected in Vibrio species isolated from molluscs harvested in Canada, between 2006 and 2012, against 19 commonly used antibiotics...
August 6, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/30081563/novel-natural-angiotensin-converting-enzyme-ace-inhibitory-peptides-derived-from-sea-cucumber-modified-hydrolysates-by-adding-exogenous-proline-and-a-study-of-their-structure%C3%A2-activity-relationship
#7
Jianpeng Li, Zunying Liu, Yuanhui Zhao, Xiaojie Zhu, Rilei Yu, Shiyuan Dong, Haohao Wu
Natural angiotensin converting enzyme (ACE)-inhibitory peptides, which are derived from marine products, are useful as antihypertensive drugs. Nevertheless, the activities of these natural peptides are relatively low, which limits their applications. The aim of this study was to prepare efficient ACE-inhibitory peptides from sea cucumber-modified hydrolysates by adding exogenous proline according to a facile plastein reaction. When 40% proline ( w / w , proline/free amino groups) was added, the modified hydrolysates exhibited higher ACE-inhibitory activity than the original hydrolysates...
August 4, 2018: Marine Drugs
https://www.readbyqxmd.com/read/30077932/cellular-responses-to-in-vitro-exposures-to-%C3%AE-blocking-pharmaceuticals-in-hard-clams-and-eastern-oysters
#8
Bushra Khan, Robert M Burgess, Sandra A Fogg, Mark G Cantwell, David R Katz, Kay T Ho
Increased consumption and improper disposal of prescription medication, such as beta (β)-blockers, contribute to their introduction into waterways and may pose threats to non-target aquatic organisms. There has been rising concern about the impacts of these prescription drugs on coastal ecosystems, especially because wastewater treatment plants are not designed to eliminate them from the discharge. Few studies have characterized the sublethal effects of β-blocker exposures in marine invertebrates. The overall aim of our research is to identify cellular responses of two commercially important filter-feeding marine bivalves, hard clams (Mercenaria mercenaria) and Eastern oysters (Crassostrea virginica), upon exposures to two β-blocker drugs, propranolol and metoprolol...
July 27, 2018: Chemosphere
https://www.readbyqxmd.com/read/30077845/spatial-distribution-of-pharmaceuticals-in-conventional-wastewater-treatment-plant-with-sludge-treatment-reed-beds-technology
#9
Katarzyna Kołecka, Magdalena Gajewska, Piotr Stepnowski, Magda Caban
Pharmaceutical residues are an emerging environmental problem. It is strongly confirmed that pharmaceuticals are present in soils and environmental waters (surface, marine and even groundwater), and that wastewater treatment plant (WWTP) effluents are the main source of pharmaceuticals in the watershed. The aim of this study was to recognize the spatial distribution and seasonal changes of selected pharmaceuticals in conventional WWTP with Sludge Treatment Reed Beds (STRBs) technology used for dewatering and stabilization of sewage sludge, because these systems have never been studied in terms of pharmaceuticals distribution or removal potential...
July 31, 2018: Science of the Total Environment
https://www.readbyqxmd.com/read/30073300/association-of-oral-contraceptives-with-drug-induced-qt-interval-prolongation-in-healthy-nonmenopausal-women
#10
Joe-Elie Salem, Pauline Dureau, Anne Bachelot, Marine Germain, Pascal Voiriot, Bruno Lebourgeois, David-Alexandre Trégouët, Jean-Sébastien Hulot, Christian Funck-Brentano
Importance: Women are at higher risk of drug-induced torsade de pointes (TdP) than men. Androgens are protective. Influence of oral contraception on drug-induced TdP and QT prolongation is controversial. Objective: To determine if the extent of sotalol-induced corrected QT (QTc) prolongation and specific T-wave morphological changes, which are biomarkers for the risk of drug-induced TdP, differ in patients according to the androgenic activity of the type of oral contraceptive (OCs) they take compared with patients who took no pills...
August 1, 2018: JAMA Cardiology
https://www.readbyqxmd.com/read/30072273/headache-as-a-reason-for-consultation-the-primary-care-perspective
#11
A López-Bravo, E Bellosta-Diago, A Viloria-Alebesque, M Marín-Gracia, J Laguna-Sarriá, S Santos-Lasaosa
INTRODUCTION: Headache is a frequent reason for consultation with primary care (PC) physicians. However, the condition is underdiagnosed and undertreated. One reason for this may be the lack of specific training on headache in PC. METHODS: We conducted a descriptive cross-sectional study of data gathered with a self-administered survey that was completed by PC physicians from our health district. We collected sociodemographic data and information on previous training in neurology and headache, and training needs...
July 30, 2018: Neurología: Publicación Oficial de la Sociedad Española de Neurología
https://www.readbyqxmd.com/read/30065225/antitumor-activity-of-quinazolinone-alkaloids-inspired-by-marine-natural-products
#12
Solida Long, Diana I S P Resende, Anake Kijjoa, Artur M S Silva, André Pina, Tamara Fernández-Marcelo, M Helena Vasconcelos, Emília Sousa, Madalena M M Pinto
Many fungal quinazolinone metabolites, which contain the methyl-indole pyrazino [1,2- b ]quinazoline-3,6-dione core, have been found to possess promising antitumor activity. The purpose of this work was to synthesize the enantiomeric pairs of two members of this quinazolinone family, to explore their potential as antitumor and their ability to revert multidrug resistance. The marine natural product fiscalin B ( 4c ), and antienantiomers ( 4b , 5b , and 5c ) were synthesized via a one-pot approach, while the syn enantiomers ( 4a , 4d , 5a , and 5d ) were synthetized by a multi-step procedure...
July 31, 2018: Marine Drugs
https://www.readbyqxmd.com/read/30063132/slow-binding-inhibition-of-mycobacterium-tuberculosis-shikimate-kinase-by-manzamine-alkaloids
#13
Johayra Simithy, Ngolui Rene Fuanta, Mansour Alturki, Judith V Hobrath, Amir E Wahba, Ivett Pina, Jnanendra Rath, Mark T Hamann, Jack DeRuiter, Douglas C Goodwin, Angela I Calderón
Tuberculosis represents a significant public health crisis. There is an urgent need for novel molecular scaffolds against this pathogen. We screened a small library of marine-derived compounds against shikimate kinase from Mycobacterium tuberculosis ( MtSK), a promising target for antitubercular drug development. Six manzamines previously shown to be active against M. tuberculosis were characterized as MtSK inhibitors: manzamine A (1), 8-hydroxymanzamine A (2), manzamine E (3), manzamine F (4), 6-deoxymanzamine X (5), and 6-cyclohexamidomanzamine A (6)...
August 14, 2018: Biochemistry
https://www.readbyqxmd.com/read/30062585/irinotecan-induced-neutropenia-is-reduced-by-oral-alkalization-drugs-analysis-using-retrospective-chart-reviews-and-the-spontaneous-reporting-database
#14
Hirofumi Hamano, Marin Mitsui, Yoshito Zamami, Kenshi Takechi, Takahiro Nimura, Naoto Okada, Keijo Fukushima, Masaki Imanishi, Masayuki Chuma, Yuya Horinouchi, Yuki Izawa-Ishizawa, Yasushi Kirino, Toshimi Nakamura, Kazuhiko Teraoka, Yasumasa Ikeda, Hiromichi Fujino, Hiroaki Yanagawa, Toshiaki Tamaki, Keisuke Ishizawa
PURPOSE: SN-38, an active metabolite of irinotecan, is reabsorbed by the intestinal tract during excretion, causing diarrhoea and neutropenia. In addition, the association between blood levels of SN-38 and neutropenia has been reported previously, and the rapid excretion of SN-38 from the intestinal tract is considered to prevent neutropenia. Oral alkalization drugs are used as prophylactic agents for suppressing SN-38 reabsorption. The relationship between oral alkalization drugs and neutropenia, however, has not been well studied...
July 31, 2018: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/30060617/manzamine-a-exerts-anticancer-activity-against-human-colorectal-cancer-cells
#15
Li-Chun Lin, Tzu-Ting Kuo, Hsin-Yi Chang, Wen-Shan Liu, Shih-Min Hsia, Tsui-Chin Huang
Marine sponges are known to produce numerous bioactive secondary metabolites as defense strategies to avoid predation. Manzamine A is a sponge-derived β-carboline-fused pentacyclic alkaloid with various bioactivities, including recently reported anticancer activity on pancreatic cancer. However, its cytotoxicity and mode of action against other tumors remain unclear. In this study, we exhibit that manzamine A reduced cell proliferation in several colorectal cancer (CRC) cell lines. To further investigate the manzamine A triggered molecular regulation, we analyzed the gene expression with microarray and revealed that pathways including cell cycle, DNA repair, mRNA metabolism, and apoptosis were dysregulated...
July 29, 2018: Marine Drugs
https://www.readbyqxmd.com/read/30060542/potential-role-of-seaweed-polyphenols-in-cardiovascular-associated-disorders
#16
REVIEW
Manuel Gómez-Guzmán, Alba Rodríguez-Nogales, Francesca Algieri, Julio Gálvez
The beneficial effects of various polyphenols with plant origins on different cardiovascular-associated disorders, such as hypertension, diabetes mellitus type 2 and metabolic syndrome are well known. Recently, marine crude-drugs are emerging as potential treatments in many noncommunicable conditions, including those involving the cardiovascular system. Among the active compounds responsible for these activities, seaweed polyphenols seem to play a key role. The aim of the present review is to summarise the current knowledge about the beneficial effects reported for edible seaweed polyphenols in the amelioration of these prevalent conditions, focusing on both preclinical and clinical studies...
July 28, 2018: Marine Drugs
https://www.readbyqxmd.com/read/30058665/biomonitoring-of-occupational-exposure-to-5-fu-by-assaying-%C3%AE-fluoro-%C3%AE-alanine-in-urine-with-a-highly-sensitive-uhplc-ms-ms-method
#17
Alice Dhersin, Benoît Atgé, Béatrice Martinez, Karine Titier, Marine Rousset, Mohamed Sidatt Cheikh El Moustaph, Catherine Verdun-Esquer, Mathieu Molimard, Antoine Villa, Mireille Canal-Raffin
5-Fluorouracil (5-FU) is one of the most widely used antineoplastic drugs handled by healthcare professionals (HCP). To monitor occupational exposure to 5-FU, a highly sensitive ESI-UHPLC-MS/MS method was developed for the assay of its main human metabolite, α-fluoro-β-alanine (FBAL), in urine. After a derivatization step, solid phase extraction was used for the urine. Good linearity (r > 0.996), precision (CV < 14.76%), and accuracy (bias < 12.16%) were achieved. The lower limit of quantification (LOQ), 20 pg ml-1, is the lowest one published to date...
July 30, 2018: Analyst
https://www.readbyqxmd.com/read/30051788/marine-derived-trichoderma-species-as-a-promising-source-of-bioactive-secondary-metabolites
#18
Dengquan Su, Lijian Ding, Shan He
Marine-derived fungi Trichoderma genus are serving as a valuable resource for structurally novel natural products encompassing a variety of chemical substances and diverse pharmacological applications. So far, about 78 metabolites had been structurally documented from the species of marine Trichoderma genus and a large proportion of these metabolites exhibited therapeutic properties with potential application in drug discovery. This mini review focuses on the structures and bioactivities of these secondary metabolites from marine-derived Trichoderma species...
July 27, 2018: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/30050506/a-new-bioactive-compound-from-the-marine-sponge-derived-streptomyces-sp-sbt348-inhibits-staphylococcal-growth-and-biofilm-formation
#19
Srikkanth Balasubramanian, Joseph Skaf, Ulrike Holzgrabe, Richa Bharti, Konrad U Förstner, Wilma Ziebuhr, Ute H Humeida, Usama R Abdelmohsen, Tobias A Oelschlaeger
Staphylococcus epidermidis , the common inhabitant of human skin and mucosal surfaces has emerged as an important pathogen in patients carrying surgical implants and medical devices. Entering the body via surgical sites and colonizing the medical devices through formation of multi-layered biofilms leads to refractory and persistent device-related infections (DRIs). Staphylococci organized in biofilms are more tolerant to antibiotics and immune responses, and thus are difficult-to-treat. The consequent morbidity and mortality, and economic losses in health care systems has strongly necessitated the need for development of new anti-bacterial and anti-biofilm-based therapeutics...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/30045524/-an-investigation-into-the-occurrence-and-removal-of-pharmaceuticals-in-colombian-wastewater
#20
A M Botero-Coy, D Martínez-Pachón, C Boix, R J Rincón, N Castillo, L P Arias-Marín, L Manrique-Losada, R Torres-Palma, A Moncayo-Lasso, F Hernández
In this work, the presence of 20 pharmaceuticals in wastewater from Colombia is investigated. Several widely consumed compounds have been detected in wastewater samples from different origins and geographical areas in Colombia. The studied pharmaceuticals included antibiotics, analgesics and anti-inflammatories, cholesterol lowering statin drugs, lipid regulators, and anti-depressants. The investigated samples were urban wastewater collected during one whole week before (influent) and after treatment (effluent) in the wastewater treatment plants (WWTPs) of Bogotá and Medellin...
November 15, 2018: Science of the Total Environment
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