116 Marine Macro- and Microalgae: An Overview
organisms and are an expression of the individuality of a species, which is defined as secondary metabolism
(Maplestone et al. 1992; Dewick 2002). This metabolism provides the majority of pharmacologically
active natural products, in contrast to the synthesis and breakdown of carbohydrates, proteins, lipids,
and nucleic acids, which are vital for the sustainability of all living organisms, and is known as primary
metabolism. Therefore, compounds involved in these pathways are known as ‘primary metabolites’. It is
the biosynthesis of secondary metabolites that provides algae with novel chemical structures possessing
unique biological activities.
Today, there are several marine-derived drugs available commercially. For example, Ecteinascidin
743 (ET743; Yondelis™; trabectedin) was isolated in very low yields from the ascidian Ecteinascidia
turbinata (Wright et al. 1990). The amount of ET743 required for advanced preclinical and clinical studies
was only achieved via large-scale aquaculture of E. turbinata in open ponds, followed by compound
isolation, as its synthesis was too complex (Manzanares et al. 2001). The production of ET743 was
carried out later by a semi-synthetic, simpler method. In 2007, ET743 was the first marine anticancer
drug to be approved in the European Union (Molinski et al. 2009) for ovarian, soft tissue sarcoma, breast,
endometrial, prostate, non-small cell lung, and paediatric cancers, and the first of a novel class of DNAbinding agents (Henríquez et al. 2005). Other examples are ziconotide (Prialt, Elan Pharmaceuticals)
and aplidine (dehydrodidemnin B). The former is a peptide first discovered in a tropical cone snail
(Conus magus) and that was approved for the treatment of pain, whereas aplidine was isolated from the
Mediterranean tunicate Aplidium albicans (Urdiales et al. 1996). Aplidine is used to treat various cancers,
including melanoma, pancreatic, head and neck, small and non-small cell lung, bladder and prostate
cancers, as well as non-Hodgkin lymphoma and acute lymphoblastic leukaemia (Henríquez et al. 2005).
Although marine algae are among the richest sources of chemically diverse natural products (Liu et
al. 2011), their potential in drug discovery has remained largely unexplored. Nevertheless, great effort has
been done in the last decades in order to investigate this resource which have led to important discoveries
that are reviewed below.
Antioxidant activity
In aerobic life, oxygen metabolism is essential for energy production but also produces toxic metabolites
such as reactive oxygen species (ROS), namely superoxide anion (O 2 ), hydroxyl radical (OH
•
), and
hydrogen peroxide (H 2 O 2 ) (Chew et al. 2008; Ko et al. 2012). In regular physiological conditions,
organisms are able to repair or reduce the damage caused by ROS through an antioxidant defence system,
including non-enzymatic and enzymatic factors (Ko et al. 2012). If these mechanisms are insufficient, the
generation of ROS can overburden the cell, which might lead to oxidative damage to macromolecules
(e.g., DNA, lipids, and proteins) and to the onset of different ailments (Kuda et al. 2005; Souza et al.
2012).
Antioxidants belong to the non-enzymatic protection defence system and can alleviate the adverse
effects of oxidative stress (Chew et al. 2008; Ko et al. 2012). Since they act as a protection mechanism
against oxidative stress, it has been put forward that antioxidant compounds may play a key role in
preventing mutations and several diseases comprising cancer, cardiovascular, inflammatory, and
neurodegenerative disorders (Kuda et al. 2005; Costa et al. 2010). Several synthetic antioxidants—
butylated hydroxyanisole (BHA; E320), butylated hydroxytoluene (BHT; E321), propyl gallate (PG;
E310), and tert-butylhydroquinone (TBHQ; E319)—have been used to avoid oxidative damage in food,
but they have also been associated with non-desirable side effects such as toxicity and carcinogenicity
(Cho et al. 2011; Souza et al. 2012). Therefore, safety issues have underlined the need for safer
compounds from natural origin to replace artificial antioxidants (Kumar et al. 2011; Cho et al. 2011).
Natural antioxidants may protect organisms against free radicals and delay the development of several
chronic diseases (Heo and Jeon 2009). For example, astaxanthin is a pigment found in natural sources
(e.g., algae, yeast, and crustacean by-products), which has been associated to a reduced risk of developing
chronic diseases, including cardiovascular disorders, cancer, and Helicobacter pylori infection (HigueraCiapara et al. 2006). Moreover, astaxanthin is a powerful antioxidant with the capacity to modulate and
stimulate the immune system (Higuera-Ciapara et al. 2006).
organisms and are an expression of the individuality of a species, which is defined as secondary metabolism
(Maplestone et al. 1992; Dewick 2002). This metabolism provides the majority of pharmacologically
active natural products, in contrast to the synthesis and breakdown of carbohydrates, proteins, lipids,
and nucleic acids, which are vital for the sustainability of all living organisms, and is known as primary
metabolism. Therefore, compounds involved in these pathways are known as ‘primary metabolites’. It is
the biosynthesis of secondary metabolites that provides algae with novel chemical structures possessing
unique biological activities.
Today, there are several marine-derived drugs available commercially. For example, Ecteinascidin
743 (ET743; Yondelis™; trabectedin) was isolated in very low yields from the ascidian Ecteinascidia
turbinata (Wright et al. 1990). The amount of ET743 required for advanced preclinical and clinical studies
was only achieved via large-scale aquaculture of E. turbinata in open ponds, followed by compound
isolation, as its synthesis was too complex (Manzanares et al. 2001). The production of ET743 was
carried out later by a semi-synthetic, simpler method. In 2007, ET743 was the first marine anticancer
drug to be approved in the European Union (Molinski et al. 2009) for ovarian, soft tissue sarcoma, breast,
endometrial, prostate, non-small cell lung, and paediatric cancers, and the first of a novel class of DNAbinding agents (Henríquez et al. 2005). Other examples are ziconotide (Prialt, Elan Pharmaceuticals)
and aplidine (dehydrodidemnin B). The former is a peptide first discovered in a tropical cone snail
(Conus magus) and that was approved for the treatment of pain, whereas aplidine was isolated from the
Mediterranean tunicate Aplidium albicans (Urdiales et al. 1996). Aplidine is used to treat various cancers,
including melanoma, pancreatic, head and neck, small and non-small cell lung, bladder and prostate
cancers, as well as non-Hodgkin lymphoma and acute lymphoblastic leukaemia (Henríquez et al. 2005).
Although marine algae are among the richest sources of chemically diverse natural products (Liu et
al. 2011), their potential in drug discovery has remained largely unexplored. Nevertheless, great effort has
been done in the last decades in order to investigate this resource which have led to important discoveries
that are reviewed below.
Antioxidant activity
In aerobic life, oxygen metabolism is essential for energy production but also produces toxic metabolites
such as reactive oxygen species (ROS), namely superoxide anion (O 2 ), hydroxyl radical (OH
•
), and
hydrogen peroxide (H 2 O 2 ) (Chew et al. 2008; Ko et al. 2012). In regular physiological conditions,
organisms are able to repair or reduce the damage caused by ROS through an antioxidant defence system,
including non-enzymatic and enzymatic factors (Ko et al. 2012). If these mechanisms are insufficient, the
generation of ROS can overburden the cell, which might lead to oxidative damage to macromolecules
(e.g., DNA, lipids, and proteins) and to the onset of different ailments (Kuda et al. 2005; Souza et al.
2012).
Antioxidants belong to the non-enzymatic protection defence system and can alleviate the adverse
effects of oxidative stress (Chew et al. 2008; Ko et al. 2012). Since they act as a protection mechanism
against oxidative stress, it has been put forward that antioxidant compounds may play a key role in
preventing mutations and several diseases comprising cancer, cardiovascular, inflammatory, and
neurodegenerative disorders (Kuda et al. 2005; Costa et al. 2010). Several synthetic antioxidants—
butylated hydroxyanisole (BHA; E320), butylated hydroxytoluene (BHT; E321), propyl gallate (PG;
E310), and tert-butylhydroquinone (TBHQ; E319)—have been used to avoid oxidative damage in food,
but they have also been associated with non-desirable side effects such as toxicity and carcinogenicity
(Cho et al. 2011; Souza et al. 2012). Therefore, safety issues have underlined the need for safer
compounds from natural origin to replace artificial antioxidants (Kumar et al. 2011; Cho et al. 2011).
Natural antioxidants may protect organisms against free radicals and delay the development of several
chronic diseases (Heo and Jeon 2009). For example, astaxanthin is a pigment found in natural sources
(e.g., algae, yeast, and crustacean by-products), which has been associated to a reduced risk of developing
chronic diseases, including cardiovascular disorders, cancer, and Helicobacter pylori infection (HigueraCiapara et al. 2006). Moreover, astaxanthin is a powerful antioxidant with the capacity to modulate and
stimulate the immune system (Higuera-Ciapara et al. 2006).