Search results for "pharmaceutical"
showing 10 items of 3243 documents
Cytotoxicity of epunctanone and four other phytochemicals isolated from the medicinal plants Garcinia epunctata and Ptycholobium contortum towards mu…
2018
Abstract Introduction Resistance of cancer cells is a serious impediment to chemotherapy and several phytochemicals are active against multi-drug resistant (MDR) phenotypes. The cytotoxicity of five naturally occurring compounds: betulin (1), mundulea lactone (2), seputhecarpan A (3), seputheisoflavone (4) and epunctanone (5) was evaluated on a panel of 9 cancer cell lines including various sensitive and drug-resistant cell lines. The modes of action of compound 5 were further investigated. Methods The resazurin reduction assay was used to evaluate cytotoxicity of samples and ferroptotic cell death induced by compound 5; caspase-Glo assay was used to detect the activation of caspases in CCR…
Discovery and validation of 2-styryl substituted benzoxazin-4-ones as a novel scaffold for rhomboid protease inhibitors
2017
Abstract Rhomboids are intramembrane serine proteases with diverse physiological functions in organisms ranging from archaea to humans. Crystal structure analysis has provided a detailed understanding of the catalytic mechanism, and rhomboids have been implicated in various disease contexts. Unfortunately, the design of specific rhomboid inhibitors has lagged behind, and previously described small molecule inhibitors displayed insufficient potency and/or selectivity. Using a computer-aided approach, we focused on the discovery of novel scaffolds with reduced liabilities and the possibility for broad structural variations. Docking studies with the E. coli rhomboid GlpG indicated that 2-styry…
Extracellular vesicles in food: Experimental evidence of their secretion in grape fruits
2017
In the last decade, the number of studies related with extracellular vesicles (EVs) has dramatically grown since their role as key part of intercellular communication has been confirmed. EVs, as transporter of distinct bioactive molecules, can take part in different physiological mechanisms and have been gaining attention as potential tools with a wide range of therapeutic effects. Whereas a high number of studies have been published related to mammalian derived EVs, including products as food source, the existence of EVs in plants still is controversial. Recent descriptions of vesicles derived from edible plants show that they might contain pharmacological active molecules. In this context…
A Simple Method to Predict Blood-Brain Barrier Permeability of Drug- Like Compounds Using Classification Trees
2017
Background: To know the ability of a compound to penetrate the blood-brain barrier (BBB) is a challenging task; despite the numerous efforts realized to predict/measure BBB passage, they still have several drawbacks. Methods: The prediction of the permeability through the BBB is carried out using classification trees. A large data set of 497 compounds (recently published) is selected to develop the tree model. Results: The best model shows an accuracy higher than 87.6% for training set; the model was also validated using 10-fold cross-validation procedure and through a test set achieving accuracy values of 86.1% and 87.9%, correspondingly. We give a brief explanation, in structural terms, o…
Recent advances on CDK inhibitors: An insight by means of in silico methods
2017
The cyclin dependent kinases (CDKs) are a small family of serine/threonine protein kinases that can act as a potential therapeutic target in several proliferative diseases, including cancer. This short review is a survey on the more recent research progresses in the field achieved by using in silico methods. All the "armamentarium" available to the medicinal chemists (docking protocols and molecular dynamics, fragment-based, de novo design, virtual screening, and QSAR) has been employed to the discovery of new, potent, and selective inhibitors of cyclin dependent kinases. The results cited herein can be useful to understand the nature of the inhibitor-target interactions, and furnish an ins…
Extracellular vesicles: small bricks for tissue repair/regeneration
2017
Extracellular vesicles (EVs) are nano-sized membrane vesicles involved in intercellular communication. EVs have pleiotropic actions in physiological and pathological conditions. The ability of EVs to transports proteins, drugs and nucleic acid, to target specific cells and to increase the stability of therapeutic cargo, make EVs interesting as new devices for the treatment of human disease. In a recently published issue of European journal of pharmaceutical sciences, Silva and colleagues reviewed the ability of EVs to modulate tissue repair and regeneration, focusing on their roles and therapeutic potential as immunomodulatory messengers. In this perspective, we discussed the open questions…
Biopiracy of natural products and good bioprospecting practice
2016
Made available in DSpace on 2018-11-26T16:27:45Z (GMT). No. of bitstreams: 0 Previous issue date: 2016-02-15 Deutsche Forschungsgemeinschaft Background: Biopiracy mainly focuses on the use of biological resources and/or knowledge of indigenous tribes or communities without allowing them to share the revenues generated out of economic exploitation or other non-monetary incentives associated with the resource/knowledge. Methods: Based on collaborations of scientists from five continents, we have created a communication platform to discuss not only scientific topics, but also more general issues with social relevance. This platform was termed 'PhytCancer -Phytotherapy to Fight Cancer' (www.phy…
Antimicrobial and Antibiofilm Activity of a Recombinant Fragment of β-Thymosin of Sea Urchin Paracentrotus lividus
2018
With the aim to obtain new antimicrobials against important pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa, we focused on antimicrobial peptides (AMPs) from Echinoderms. An example of such peptides is Paracentrin 1 (SP1), a chemically synthesised peptide fragment of a sea urchin thymosin. In the present paper, we report on the biological activity of a Paracentrin 1 derivative obtained by recombination. The recombinant paracentrin RP1, in comparison to the synthetic SP1, is 22 amino acids longer and it was considerably more active against the planktonic forms of S. aureus ATCC 25923 and P. aeruginosa ATCC 15442 at concentrations of 50 µ
Solid nanoemulsion as antigen and immunopotentiator carrier for transcutaneous immunization
2015
Imiquimod, a toll-like receptor 7 (TLR7) agonist, is an active pharmaceutical ingredient (API) established for the topical treatment of several dermal cancerous and precancerous skin lesions. Within this work, the immunostimulatory effect of imiquimod is further exploited in a transcutaneous immunization (TCI) approach based on a solid nanoemulsion (SN) formulation. SN contains a combination of imiquimod with the model peptide antigen SIINFEKL as a novel approach to omit needle and syringe and optimize dermal antigen administration. Excipients including sucrose fatty acid esters and the pharmaceutically acceptable oils MCT (middle chain triglycerides), avocado oil, jojoba wax and squalene a…
From Genesis to Revelation: The Role of Inflammatory Mediators in Chronic Respiratory Diseases and their Control by Nucleic Acid-based Drugs.
2015
Asthma, chronic obstructive pulmonary disease, cystic fibrosis, and idiopathic pulmonary fibrosis, are among the most common chronic diseases and their prevalence is increasing. Each of these diseases is characterized by the secretion of cytokines and pro-inflammatory molecules which are thought to play a critical role in their pathogenesis. Moreover, immune cells, particularly neutrophils, macrophages and dendritic cells as well structural cells such as epithelial and airway smooth muscle cells are also involved in the pathogenic cycle of these diseases. There is a pressing need for the development of new therapies for these pulmonary diseases, particularly as no existing treatment has bee…