Cancer is a multistage process resulting in an uncontrolled and abrupt division of cells and is one of the leading causes of mortality. The cases reported and the predictions for the near future are ...unthinkable. Food and Drug Administration data showed that 40% of the approved molecules are natural compounds or inspired by them, from which, 74% are used in anticancer therapy. In fact, natural products are viewed as more biologically friendly, that is less toxic to normal cells. In this review, the most recent and successful cases of secondary metabolites, including alkaloid, diterpene, triterpene and polyphenolic type compounds, with great anticancer potential are discussed. Focusing on the ones that are in clinical trial development or already used in anticancer therapy, therefore successful cases such as paclitaxel and homoharringtonine (in clinical use), curcumin and ingenol mebutate (in clinical trials) will be addressed. Each compound's natural source, the most important steps in their discovery, their therapeutic targets, as well as the main structural modifications that can improve anticancer properties will be discussed in order to show the role of plants as a source of effective and safe anticancer drugs.
In recent years, more attention has been paid to natural sources of antioxidants. Flavonoids are natural substances synthesized in several parts of plants that exhibit a high antioxidant capacity. ...They are a large family, presenting several classes based on their basic structure. Flavonoids have the ability to control the accumulation of reactive oxygen species (ROS) via scavenger ROS when they are formed. Therefore, these antioxidant compounds have an important role in plant stress tolerance and a high relevance in human health, mainly due to their anti-inflammatory and antimicrobial properties. In addition, flavonoids have several applications in the food industry as preservatives, pigments, and antioxidants, as well as in other industries such as cosmetics and pharmaceuticals. However, flavonoids application for industrial purposes implies extraction processes with high purity and quality. Several methodologies have been developed aimed at increasing flavonoid extraction yield and being environmentally friendly. This review presents the most abundant natural flavonoids, their structure and chemical characteristics, extraction methods, and biological activity.
Seaweeds have received huge interest in recent years given their promising potentialities. Their antioxidant, anti-inflammatory, antitumor, hypolipemic, and anticoagulant effects are among the most ...renowned and studied bioactivities so far, and these effects have been increasingly associated with their content and richness in both primary and secondary metabolites. Although primary metabolites have a pivotal importance such as their content in polysaccharides (fucoidans, agars, carragenans, ulvans, alginates, and laminarin), recent data have shown that the content in some secondary metabolites largely determines the effective bioactive potential of seaweeds. Among these secondary metabolites, phenolic compounds feature prominently. The present review provides the most remarkable insights into seaweed research, specifically addressing its chemical composition, phytopharmacology, and cosmetic applications.
Isolation, finding or discovery of novel anticancer agents is very important for cancer treatment, and seaweeds are one of the largest producers of chemically active metabolites with valuable ...cytotoxic properties, and therefore can be used as new chemotherapeutic agents or source of inspiration to develop new ones. Identification of the more potent and selective anticancer components isolated from brown, green and red seaweeds, as well as studies of their mode of action is very attractive and constitute a small but relevant progress for pharmacological applications. Several researchers have carried out in vitro and in vivo studies in various cell lines and have disclosed the active metabolites among the terpenoids, including carotenoids, polyphenols and alkaloids that can be found in seaweeds. In this review the type of metabolites and their cytotoxic or antiproliferative effects will be discussed additionally their mode of action, structure-activity relationship and selectivity will also be revealed. The diterpene dictyolactone, the sterol cholest-5-en-3β,7α-diol and the halogenated monoterpene halomon are among the reported compounds, the ones that present sub-micromolar cytotoxicity. Additionally, one dimeric sesquiterpene of the cyclolaurane-type, three bromophenols and one halogenated monoterpene should be emphasized because they exhibit half maximal inhibitory concentration (IC
) values between 1⁻5 µM against several cell lines.
Hypertension and obesity are two significant factors that contribute to the onset and exacerbation of a cascade of mechanisms including activation of the sympathetic and renin-angiotensin systems, ...oxidative stress, release of inflammatory mediators, increase of adipogenesis and thus promotion of systemic dysfunction that leads to clinical manifestations of cardiovascular diseases. Seaweeds, in addition to their use as food, are now unanimously acknowledged as an invaluable source of new natural products that may hold noteworthy leads for future drug discovery and development, including in the prevention and/or treatment of the cardiovascular risk factors. Several compounds including peptides, phlorotannins, polysaccharides, carotenoids, and sterols, isolated from brown, red and green macroalgae exhibit significant anti-hypertensive and anti-obesity properties. This review will provide a comprehensive overview of the recent advances on bioactive pure compounds isolated from different seaweed sources focusing on their potential use as drugs to treat or prevent hypertension and obesity. On the other hand, although it is obvious that macroalgae represent promising sources of antihypertensive and anti-obesity compounds, it is also clear that further efforts are required to fully understand their cellular mechanisms of action, to establish structure-inhibition relationships and mainly to evaluate them in pre-clinical and clinical trials.
Inflammation is an organism's response to chemical or physical injury. It is split into acute and chronic inflammation and is the last, most significant cause of death worldwide. Nowadays, according ...to the World Health Organization (WHO), the greatest threat to human health is chronic disease. Worldwide, three out of five people die from chronic inflammatory diseases such as stroke, chronic respiratory diseases, heart disorders, and cancer. Nowadays, anti-inflammatory drugs (steroidal and non-steroidal, enzyme inhibitors that are essential in the inflammatory process, and receptor antagonists, among others) have been considered as promising treatments to be explored. However, there remains a significant proportion of patients who show poor or incomplete responses to these treatments or experience associated severe side effects. Seaweeds represent a valuable resource of bioactive compounds associated with anti-inflammatory effects and offer great potential for the development of new anti-inflammatory drugs. This review presents an overview of specialized metabolites isolated from seaweeds with in situ and in vivo anti-inflammatory properties. Phlorotannins, carotenoids, sterols, alkaloids, and polyunsaturated fatty acids present significant anti-inflammatory effects given that some of them are involved directly or indirectly in several inflammatory pathways. The majority of the isolated compounds inhibit the pro-inflammatory mediators/cytokines. Studies have suggested an excellent selectivity of chromene nucleus towards inducible pro-inflammatory COX-2 than its constitutive isoform COX-1. Additional research is needed to understand the mechanisms of action of seaweed's compounds in inflammation, given the production of sustainable and healthier anti-inflammatory agents.
Being naturally enriched in key nutrients and in various health-promoting compounds, seaweeds represent promising candidates for the design of functional foods. Soluble dietary fibers, peptides, ...phlorotannins, lipids and minerals are macroalgae's major compounds that can hold potential in high-value food products derived from macroalgae, including those directed to the cardiovascular-health promotion. This manuscript revises available reported data focusing the role of diet supplementation of macroalgae, or extracts enriched in bioactive compounds from macroalgae origin, in targeting modifiable markers of cardiovascular diseases (CVDs), like dyslipidemia, oxidative stress, vascular inflammation, hypertension, hypercoagulability and activation of the sympathetic and renin-angiotensin systems, among others. At last, the review also describes several products that have been formulated with the use of whole macroalgae or extracts, along with their claimed cardiovascular-associated benefits.
Fucales are an order within the Phaeophyceae that include most of the common littoral seaweeds in temperate and subtropical coastal regions. Many species of this order have long been a part of human ...culture with applications as food, feedand remedies in folk medicine. Apart from their high nutritional value, these seaweeds are also a well-known reservoir of multiple bioactive compounds with great industrial interest. Among them, phlorotannins, a unique and diverse class of brown algae-exclusive phenolics, have gathered much attention during the last few years due to their numerous potential health benefits. However, due to their complex structural features, combined with the scarcity of standards, it poses a great challenge to the identification and characterization of these compounds, at least with the technology currently available. Nevertheless, much effort has been taken towards the elucidation of the structural features of phlorotannins, which have resulted in relevant insights into the chemistry of these compounds. In this context, this review addresses the major contributions and technological advances in the field of phlorotannins extraction and characterization, with a particular focus on Fucales.
Microwave irradiation has become a popular heating technique in organic synthesis, mainly due to its short reaction times, solventless reactions, and, sometimes, higher yields. Additionally, ...microwave irradiation lowers energy consumption and, consequently, is ideal for optimization processes. Moreover, there is evidence that microwave irradiation can improve the regioselectivity and stereoselectivity aspects of vital importance in synthesizing bioactive compounds. These crucial features of microwave irradiation contribute to its inclusion in green chemistry procedures. Since 2003, the use of microwave-assisted organic synthesis has become common in our laboratory, making our group one of the first Portuguese research groups to implement this heating source in organic synthesis. Our achievements in the transformation of heterocyclic compounds, such as (
/
)-3-styryl-4
-chromen-4-ones, (
)-3-(2-hydroxyphenyl)-4-styryl-1
-pyrazole, (
)-2-(4-arylbut-1-en-3-yn-1-yl)-4
-chromen-4-ones, or (
)-2-2-(5-aryl-2-methyl-2
-1,2,3-triazol-4-yl)vinyl-4
-chromen-4-ones, will be discussed in this review, highlighting the benefits of microwave irradiation use in organic synthesis.
Macroalgae are increasingly viewed as a source of secondary metabolites with great potential for the development of new drugs. In this development, in vitro studies are only the first step in a long ...process, while in vivo studies and clinical trials are the most revealing stages of the true potential and limitations that a given metabolite may have as a new drug. This literature review aims to give a critical overview of the secondary metabolites that reveal the most interesting results in these two steps. Phlorotannins show great pharmaceutical potential in in vivo models and, among the several examples, the anti-dyslipidemia activity of dieckol must be highlighted because it was more effective than lovastatin in an in vivo model. The IRLIIVLMPILMA tridecapeptide that exhibits an in vivo level of activity similar to the hypotensive clinical drug captopril should still be stressed, as well as griffithsin which showed such stunning results over a variety of animal models and which will probably move onto clinical trials soon. Regarding clinical trials, studies with pure algal metabolites are scarce, limited to those carried out with kahalalide F and fucoxanthin. The majority of clinical trials currently aim to ascertain the effect of algae consumption, as extracts or fractions, on obesity and diabetes.
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