Tiago H. Silva

Plant derived and dietary phenolic antioxidants: anticancer properties.

In this paper, a review of the literature on the phenolic compounds with anticancer activity published between 2008 and 2012 is presented. In this overview only phenolic antioxidant compounds that display significant anticancer activity have been described. In the first part of this review, the oxidative and nitrosative stress relation with cancer are described. In the second part, the plant-derived food extracts, containing identified phenolic antioxidants, the phenolic antioxidants isolated from plants and plant-derived food or commercially available and the synthetic ones, along with the type of cancer and cells where they exert anticancer activity, are described and summarized in tables. The principal mechanisms for their anti-proliferative effects were also described. Finally, a critical analysis of the studies and directions for future research are included in the conclusion.

Materials of marine origin: a review on polymers and ceramics of biomedical interest

Abstract Marine organisms are constituted by materials with a vast range of properties and characteristics that may justify their potential application within the biomedical field. Moreover, assuring the sustainable exploitation of natural marine resources, the valorisation of residues from marine origin, like those obtained from food processing, constitutes a highly interesting platform for development of novel biomaterials, with both economic and environmental benefits. In this perspective, an increasing number of different types of compounds are being isolated from aquatic organisms and transformed into profitable products for health applications, including controlled drug delivery and tissue engineering devices. This report reviews the work that is being developed on the isolation and characterisation of some polysaccharides, proteins, glycosaminoglycans and ceramics from marine raw materials. Emphasis is given to agar, alginates, carrageenans, chitin and chitosan, among other polysaccharides, collagen, glycosaminoglycans such as chondroitin sulphate, heparin and hyaluronic acid, calcium phosphorous compounds and biosilica. Finally, this report ends by reviewing the application of the previously mentioned materials on specific biomedical applications, in particular their participation on the development of controlled drug delivery systems and tissue engineering scaffolds.

Chromone, a Privileged Scaffold for the Development of Monoamine Oxidase Inhibitors

Two series of novel chromone derivatives were synthesized and investigated for their ability to inhibit the activity of monoamine oxidase. The SAR data indicate that chromone derivatives with substituents in position 3 of γ-pyrone nucleus act preferably as MAO-B inhibitors, with IC(50) values in the nanomolar to micromolar range. Almost all chromone 3-carboxamides display selectivity toward MAO-B. Identical substitutions on position 2 of γ-pyrone nucleus result in complete loss of activity in both isoforms (chromones 2-12 except 3 and 5). Notably, chromone (19) exhibits an MAO-B IC(50) of 63 nM, greater than 1000-fold selectivity over MAO-A, and behaves as a quasi-reversible inhibitor. Docking experiments onto the MAO binding of the most active compound highlight different interaction patterns among the isoforms A and B. The differential analysis of the solvation effects among the chromone isomers gave additional insight about the superior outline of the 3-substituted chromone derivatives.

Lipophilic Caffeic and Ferulic Acid Derivatives Presenting Cytotoxicity against Human Breast Cancer Cells

In the present work, lipophilic caffeic and ferulic acid derivatives were synthesized, and their cytotoxicity on cultured breast cancer cells was compared. A total of six compounds were initially evaluated: caffeic acid (CA), hexyl caffeate (HC), caffeoylhexylamide (HCA), ferulic acid (FA), hexyl ferulate (HF), and feruloylhexylamide (HFA). Cell proliferation, cell cycle progression, and apoptotic signaling were investigated in three human breast cancer cell lines, including estrogen-sensitive (MCF-7) and insensitive (MDA-MB-231 and HS578T). Furthermore, direct mitochondrial effects of parent and modified compounds were investigated by using isolated liver mitochondria. The results indicated that although the parent compounds presented no cytotoxicity, the new compounds inhibited cell proliferation and induced cell cycle alterations and cell death, with a predominant effect on MCF-7 cells. Interestingly, cell cycle data indicates that effects on nontumor BJ fibroblasts were predominantly cytostatic and not cytotoxic. The parent compounds and derivatives also promoted direct alterations on hepatic mitochondrial bioenergetics, although the most unexpected and never before reported one was that FA induces the mitochondrial permeability transition. The results show that the new caffeic and ferulic acid lipophilic derivatives show increased cytotoxicity toward human breast cancer cell lines, although the magnitude and type of effects appear to be dependent on the cell type. Mitochondrial data had no direct correspondence with effects on intact cells suggesting that this organelle may not be a critical component of the cellular effects observed. The data provide a rational approach to the design of effective cytotoxic lipophilic hydroxycinnamic derivatives that in the future could be profitably applied for chemopreventive and/or chemotherapeutic purposes.

Marine Origin Collagens and Its Potential Applications

Collagens are the most abundant high molecular weight proteins in both invertebrate and vertebrate organisms, including mammals, and possess mainly a structural role, existing different types according with their specific organization in distinct tissues. From this, they have been elected as one of the key biological materials in tissue regeneration approaches. Also, industry is constantly searching for new natural sources of collagen and upgraded methodologies for their production. The most common sources are from bovine and porcine origin, but other ways are making their route, such as recombinant production, but also extraction from marine organisms like fish. Different organisms have been proposed and explored for collagen extraction, allowing the sustainable production of different types of collagens, with properties depending on the kind of organism (and their natural environment) and extraction methodology. Such variety of collagen properties has been further investigated in different ways to render a wide range of applications. The present review aims to shed some light on the contribution of marine collagens for the scientific and technological development of this sector, stressing the opportunities and challenges that they are and most probably will be facing to assume a role as an alternative source for industrial exploitation.

Alzheimer's disease, enzyme targets and drug discovery struggles: From natural products to drug prototypes

Alzheimers disease (AD) is an incapacitating neurodegenerative disease that slowly destroys brain cells. This disease progressively compromises both memory and cognition, culminating in a state of full dependence and dementia. Currently, AD is the main cause of dementia in the elderly and its prevalence in the developed world is increasing rapidly. Classic drugs, such as acetylcholinesterase inhibitors (AChEIs), fail to decline disease progression and display several side effects that reduce patients adhesion to pharmacotherapy. The past decade has witnessed an increasing focus on the search for novel AChEIs and new putative enzymatic targets for AD, like β- and γ-secretases, sirtuins, caspase proteins and glycogen synthase kinase-3 (GSK-3). In addition, new mechanistic rationales for drug discovery in AD that include autophagy and synaptogenesis have been discovered. Herein, we describe the state-of-the-art of the development of recent enzymatic inhibitors and enhancers with therapeutic potential on the treatment of AD.

Marine algae sulfated polysaccharides for tissue engineering and drug delivery approaches.

Biomedical field is constantly requesting for new biomaterials, with innovative properties. Natural polymers appear as materials of election for this goal due to their biocompatibility and biodegradability. In particular, materials found in marine environment are of great interest since the chemical and biological diversity found in this environment is almost uncountable and continuously growing with the research in deeper waters. Moreover, there is also a slower risk of these materials to pose illnesses to humans. In particular, sulfated polysaccharides can be found in marine environment, in different algae species. These polysaccharides don’t have equivalent in the terrestrial plants and resembles the chemical and biological properties of mammalian glycosaminoglycans. In this perspective, are receiving growing interest for application on health-related fields. On this review, we will focus on the biomedical applications of marine algae sulfated polymers, in particular on the development of innovative systems for tissue engineering and drug delivery approaches.

Alzheimer’s Disease, Cholesterol, and Statins: The Junctions of Important Metabolic Pathways

Recent years have seen a significant increase in published data supporting the positive effects of statins on neurodegenerative diseases, in particular on Alzheimers disease. Statins show neuroprotective activity by a combination of different cellular and systemic mechanisms that are based on the inhibition of the biosynthesis of cholesterol and isoprenoid by-products. The promising results obtained in vivo and in epidemiological studies are generally not in accordance with those of placebo-controlled randomized clinical trials. Nevertheless, these results make statins valuable assets for disease prevention rather than therapeutic agents for use when disease symptoms are already displayed. Thus, the modulation of midlife cholesterol and/or statin administration prior to the appearance of dementia or cognitive impairment may have a better long-term outcome.

The use of ionic liquids in the processing of chitosan/silk hydrogels for biomedical applications

Natural polymers are adequate renewable resources for the processability of well-defined architectures for several applications. Combinations of polysaccharides and proteins may mimic the naturally occurring environment of certain tissues. The main goal of this work renders the application of green chemistry principles, namely the use of ionic liquids (ILs) and biorenewable sources, such as chitosan (CHT) and silk fibroin (SF), to process new hydrogel-based constructs. Although the solubilization of both materials in ILs has been studied individually, this work reports, for the first time, the role of ILs as solvent, for the production of hydrogels from blends of chitosan and silk fibroin (CSF). These systems offer the advantage of being homogeneous and presenting easy and short dissolution time of both biomacromolecules. Moreover, the use of chitosan obtained from α- and β-chitin allowed the production of blended hydrogels with distinct physical–chemical properties. In vitro assays demonstrated that these hydrogels supported the adhesion and growth of primary human dermal fibroblasts. Taken these properties together, the CSF hydrogels might be promising biomaterials to be explored for skin tissue engineering approaches.

Nanostructured natural-based polyelectrolyte multilayers to agglomerate chitosan particles into scaffolds for tissue engineering

The layer-by-layer (LbL) deposition technique is a self-assembly process that allows the coating of materials surface with nanostructured layers of polyelectrolytes, allowing to control several surface properties. This technique presents some advantages when compared with other thin film assembly techniques, like having the possibility to coat surfaces with complex geometries in mild conditions or to incorporate active compounds. Tissue engineering (TE) involves typically the use of porous biodegradable scaffolds for the temporary support of cells. Such structures can be produced by agglomeration of microspheres that needs to be fixed into a three-dimensional (3D) structure. In this work we suggest the use of LbL to promote such mechanical fixation in free-formed microspheres assemblies and simultaneously to control the properties of its surface. For the proof of concept the biological performance of chitosan/alginate multilayers is first investigated in two-dimensional (2D) models in which the attachment and proliferation of L929 and ATDC5 cells are studied in function of the number of layers and the nature of the final layer. Scaffolds prepared by agglomeration of chitosan particles using the same multilayered system were processed and characterized; it was found that they could support the attachment and proliferation of ATDC5 cells. This study suggests that LbL can be used as a versatile methodology to prepare scaffolds by particle agglomeration that could be suitable for TE applications.