Part F | 29.1
712 Part F Marine Derived Metabolites
29.1 Overview and Current Status
29.1.1 The Marine Environment,
a Unique and Prolific Source
of Bioactive Natural Products
A natural product can be defined as a compound that is
present in or produced by living systems in nature and
is not artificial or man-made [29.1]. Natural products
are often structurally complex compounds that possess
a well-defined spatial orientation. Their activity due to
chemical compounds has evolved to interact efficiently
with their biological targets and provides important
clues for drug discovery. Many of these compounds
exert their bioactive properties as secondary metabolites, in ecological, defensive, antifeedant, attractant,
and pheromone roles. In nature, as in the marine environment, every natural product is believed to have
emerged as a result of exerted pressure on the first living organisms from the sea, more than 3500 million
years ago, under a context of evolution which enables
marine organisms to survive in an extremely competitive milieu, such as extreme temperatures, changes
in salinity and pressure, among others [29.2]. In this
way, molecules acquired biochemical specialization
and diverse metabolic roles and functions, as is now
known. All these characteristics and properties have
created conditions with a high degree of chemical
diversity and a rich source of biologically active natural products found in marine environments, which
are of remarkable novelty [29.3] as medicines. Expectations are high with respect to the ocean as the
most chemically and biologically rich environment on
the planet [29.4] is also the last frontier, unexplored
and unexploited. A great number of these biologically
active molecules from marine natural products has developed roles as biological receptors in a co-evolution
process and allow interaction with human proteins, expressed lately as drug leads. The marine environment
is characterized by physical and chemical properties
that are markedly different from those of the terrestrial
environment [29.5]. For instance, marine natural products have higher molecular weights than their synthetic
counterparts and are characterized as having fewer nitrogen, halogen, or sulfur atoms, and a larger proportion
of oxygen atoms, and are sterically complex (more
bridgehead atoms, rings, and chiral centers) [29.6].
As a consequence, the development and evolution of
biosynthetic pathways displayed specialized molecules,
as defense, deterrents, ferhormones, and for hunting
strategies. This wide range of bioactivities produced by
compounds of marine organisms emphasizes the great
potential of compounds for biomedical applications,
which has encouraged further large-scale programs of
bioprospection and systematic screening of marine organisms. Recent technological and scientific advances
in the sciences have led to a multitude of discoveries of carbon skeletons and molecules hitherto unseen
on land [29.4] and to contribute to the discovery of
new functionalities for common targets of human diseases, and consequently new drugs from the marine
environment.
Considering that unexplored marine organisms harbor the widest biological and chemical diversity, the
possibilities to discover novel structures (to date, more
than 21 855 compounds have been discovered) with
novel modes of action, are high [29.7]. The uniqueness
of marine natural products lends them to applications
as preclinical and clinical lead compounds for the
treatment of the most important challenge to human
diseases, viz, cancer and other important neurodegenerative diseases. Presently, marine natural products and
their metabolites are recognized as biologically active
leads for therapeutic agents.
The field of marine natural products is now close to
50 years old. Thousands of natural products have been
described through academic and industrial screening
efforts for pharmaceutical candidates, but with limited success in certain targets, such as cancer, pain,
or inflammation [29.8]. The natural products platform
has attracted the interest of the pharmaceutical industry because of the low number of new developments
in biopharmaceuticals on the market and the increasing incidence of recurrent diseases. The need for new
drugs to face current and rare diseases, viz, new classes
of antibiotics [29.9], many cancers, and chronic and
neurodegenerative diseases is still lacking effective
treatments, mainly for vulnerable populations in developing countries, which are rich in their potential of
natural products. In spite of these evident needs, the
number of drugs from the sea represents only a discrete number of marine-derived compounds that have
been approved for the treatment of human disease, such
as: Vidarabine (Ara-A) and cytarabine (Ara-C), which
were derived and inspired by nucleosides found in marine sponges, ziconotide (Prialt1), a synthetic version of
omega-conotoxin, produced by a tropical marine cone
snail, and approved for the treatment of chronic pain;
trabectedin (Yondelis) found in a tunicate was approved
as an anticancer compound in the European Union.
712 Part F Marine Derived Metabolites
29.1 Overview and Current Status
29.1.1 The Marine Environment,
a Unique and Prolific Source
of Bioactive Natural Products
A natural product can be defined as a compound that is
present in or produced by living systems in nature and
is not artificial or man-made [29.1]. Natural products
are often structurally complex compounds that possess
a well-defined spatial orientation. Their activity due to
chemical compounds has evolved to interact efficiently
with their biological targets and provides important
clues for drug discovery. Many of these compounds
exert their bioactive properties as secondary metabolites, in ecological, defensive, antifeedant, attractant,
and pheromone roles. In nature, as in the marine environment, every natural product is believed to have
emerged as a result of exerted pressure on the first living organisms from the sea, more than 3500 million
years ago, under a context of evolution which enables
marine organisms to survive in an extremely competitive milieu, such as extreme temperatures, changes
in salinity and pressure, among others [29.2]. In this
way, molecules acquired biochemical specialization
and diverse metabolic roles and functions, as is now
known. All these characteristics and properties have
created conditions with a high degree of chemical
diversity and a rich source of biologically active natural products found in marine environments, which
are of remarkable novelty [29.3] as medicines. Expectations are high with respect to the ocean as the
most chemically and biologically rich environment on
the planet [29.4] is also the last frontier, unexplored
and unexploited. A great number of these biologically
active molecules from marine natural products has developed roles as biological receptors in a co-evolution
process and allow interaction with human proteins, expressed lately as drug leads. The marine environment
is characterized by physical and chemical properties
that are markedly different from those of the terrestrial
environment [29.5]. For instance, marine natural products have higher molecular weights than their synthetic
counterparts and are characterized as having fewer nitrogen, halogen, or sulfur atoms, and a larger proportion
of oxygen atoms, and are sterically complex (more
bridgehead atoms, rings, and chiral centers) [29.6].
As a consequence, the development and evolution of
biosynthetic pathways displayed specialized molecules,
as defense, deterrents, ferhormones, and for hunting
strategies. This wide range of bioactivities produced by
compounds of marine organisms emphasizes the great
potential of compounds for biomedical applications,
which has encouraged further large-scale programs of
bioprospection and systematic screening of marine organisms. Recent technological and scientific advances
in the sciences have led to a multitude of discoveries of carbon skeletons and molecules hitherto unseen
on land [29.4] and to contribute to the discovery of
new functionalities for common targets of human diseases, and consequently new drugs from the marine
environment.
Considering that unexplored marine organisms harbor the widest biological and chemical diversity, the
possibilities to discover novel structures (to date, more
than 21 855 compounds have been discovered) with
novel modes of action, are high [29.7]. The uniqueness
of marine natural products lends them to applications
as preclinical and clinical lead compounds for the
treatment of the most important challenge to human
diseases, viz, cancer and other important neurodegenerative diseases. Presently, marine natural products and
their metabolites are recognized as biologically active
leads for therapeutic agents.
The field of marine natural products is now close to
50 years old. Thousands of natural products have been
described through academic and industrial screening
efforts for pharmaceutical candidates, but with limited success in certain targets, such as cancer, pain,
or inflammation [29.8]. The natural products platform
has attracted the interest of the pharmaceutical industry because of the low number of new developments
in biopharmaceuticals on the market and the increasing incidence of recurrent diseases. The need for new
drugs to face current and rare diseases, viz, new classes
of antibiotics [29.9], many cancers, and chronic and
neurodegenerative diseases is still lacking effective
treatments, mainly for vulnerable populations in developing countries, which are rich in their potential of
natural products. In spite of these evident needs, the
number of drugs from the sea represents only a discrete number of marine-derived compounds that have
been approved for the treatment of human disease, such
as: Vidarabine (Ara-A) and cytarabine (Ara-C), which
were derived and inspired by nucleosides found in marine sponges, ziconotide (Prialt1), a synthetic version of
omega-conotoxin, produced by a tropical marine cone
snail, and approved for the treatment of chronic pain;
trabectedin (Yondelis) found in a tunicate was approved
as an anticancer compound in the European Union.