Drugs and Le
711
Part F | 29.1
29. Drugs and Leads from the Ocean
Through Biotechnology
José de Jesús Paniagua-Michel, Jorge Olmos-Soto, Eduardo Morales-Guerrero
The ocean’s uniqueness represents an excellent
source of resources and inspiration of diverse marine natural products with novel chemical entities
and leads for the development of pharmaceutical agents. During the last 10 years, interest in
research and development by the scientific community in this niche have continued as evidenced
from joint ventures between academics, mainly
partnered with industry. Drugs of marine origin
that have now been approved represent excellent
and novel alternatives for the following therapies and disease treatments. For neuropathic pain,
a synthetic version of omega-conotoxin, produced
by the tropical marine Conus snail is already on the
pharmaceutical market. The ecteinascidins (ET-743)
are marine alkaloid, anticancer agents isolated
from Ecteinascidia turbinate, a colonial tunicate
found in the Caribbean and Mediterranean Sea,
and are successfully used for soft tissue sarcoma
and relapsed ovarian cancer. The synthetic pyrimidine nucleoside Cytarabine, was originally isolated
from the Caribbean sponge Tethya crypta, and approved as a chemotherapeutic to treat different
forms of leukemia (e.g., meningeal leukemia, lymphocytic leukemia). From this marine sponge, also
the synthetic purine nucleoside analog, Vidarabine, was developed as an antiviral drug against
the herpes simplex virus and the varicella-zoster
virus for the treatment of epithelial keratitis, viz,
ophthalmic applications. In 2012, squalamine was
been awarded Fast Track designation by the US
Food and Drug Administration (FDA) for the potential treatment of the wet form of macular
degeneration. These successful advances have had
to overcome difficulties characteristic of marine
natural products to become drugs, viz, sustainable sources, structural complexity, and toxicity,
the same as the marine molecules in preclinical
and clinical trials. In this chapter, the current advances and modern approaches of marine natural
products and respective bioactive metabolites with
29.1 Overview and Current Status ................ 712
29.1.1 The Marine Environment,
a Unique and Prolific Source
of Bioactive Natural Products...... 712
29.2 Approved Marine Drugs
as Pharmaceuticals .............................. 713
29.2.1 !-Conotoxin MVIIA: An Analgesic
for Neuropathic Pain ................. 713
29.2.2 Ecteinascidins:
A Therapy for Soft Tissue Sarcoma 714
29.2.3 Cytarabine to Treat
Meningeal Leukemia; Vidarabine,
An Ophthalmic,
Non-Corticosteroid Antiviral ....... 714
29.2.4 Marine Natural Products
in Advanced Clinical Trials .......... 716
29.3 Marine Natural Products –
Overcoming Hurdles ............................. 718
29.4 Quo Vadis? Marine Natural Products
and Clinical Trials ................................ 718
29.4.1 (C)-Discodermolide ................... 719
29.5 Marine Natural Products:
New and Recurrent Challenges ............. 720
29.5.1 Facing Supply Obstacles:
Advances and Strategies............. 720
29.5.2 Marine Natural Products:
Paradigms, Genomics,
and Biosynthesis Exemplified..... 721
29.5.3 Marine Natural Products
at the Crossroad Between
Functional Foods and Pharma .... 723
References................................................... 724
potential and real functions as drugs leads are
succinctly reviewed and particularly exemplified.
An important aspect of this chapter is the analysis of marine natural products in relation to
new paradigms and particularities of other disciplines, such as genomics, combinatorial chemistry,
biosynthesis, and functional foods.
711
Part F | 29.1
29. Drugs and Leads from the Ocean
Through Biotechnology
José de Jesús Paniagua-Michel, Jorge Olmos-Soto, Eduardo Morales-Guerrero
The ocean’s uniqueness represents an excellent
source of resources and inspiration of diverse marine natural products with novel chemical entities
and leads for the development of pharmaceutical agents. During the last 10 years, interest in
research and development by the scientific community in this niche have continued as evidenced
from joint ventures between academics, mainly
partnered with industry. Drugs of marine origin
that have now been approved represent excellent
and novel alternatives for the following therapies and disease treatments. For neuropathic pain,
a synthetic version of omega-conotoxin, produced
by the tropical marine Conus snail is already on the
pharmaceutical market. The ecteinascidins (ET-743)
are marine alkaloid, anticancer agents isolated
from Ecteinascidia turbinate, a colonial tunicate
found in the Caribbean and Mediterranean Sea,
and are successfully used for soft tissue sarcoma
and relapsed ovarian cancer. The synthetic pyrimidine nucleoside Cytarabine, was originally isolated
from the Caribbean sponge Tethya crypta, and approved as a chemotherapeutic to treat different
forms of leukemia (e.g., meningeal leukemia, lymphocytic leukemia). From this marine sponge, also
the synthetic purine nucleoside analog, Vidarabine, was developed as an antiviral drug against
the herpes simplex virus and the varicella-zoster
virus for the treatment of epithelial keratitis, viz,
ophthalmic applications. In 2012, squalamine was
been awarded Fast Track designation by the US
Food and Drug Administration (FDA) for the potential treatment of the wet form of macular
degeneration. These successful advances have had
to overcome difficulties characteristic of marine
natural products to become drugs, viz, sustainable sources, structural complexity, and toxicity,
the same as the marine molecules in preclinical
and clinical trials. In this chapter, the current advances and modern approaches of marine natural
products and respective bioactive metabolites with
29.1 Overview and Current Status ................ 712
29.1.1 The Marine Environment,
a Unique and Prolific Source
of Bioactive Natural Products...... 712
29.2 Approved Marine Drugs
as Pharmaceuticals .............................. 713
29.2.1 !-Conotoxin MVIIA: An Analgesic
for Neuropathic Pain ................. 713
29.2.2 Ecteinascidins:
A Therapy for Soft Tissue Sarcoma 714
29.2.3 Cytarabine to Treat
Meningeal Leukemia; Vidarabine,
An Ophthalmic,
Non-Corticosteroid Antiviral ....... 714
29.2.4 Marine Natural Products
in Advanced Clinical Trials .......... 716
29.3 Marine Natural Products –
Overcoming Hurdles ............................. 718
29.4 Quo Vadis? Marine Natural Products
and Clinical Trials ................................ 718
29.4.1 (C)-Discodermolide ................... 719
29.5 Marine Natural Products:
New and Recurrent Challenges ............. 720
29.5.1 Facing Supply Obstacles:
Advances and Strategies............. 720
29.5.2 Marine Natural Products:
Paradigms, Genomics,
and Biosynthesis Exemplified..... 721
29.5.3 Marine Natural Products
at the Crossroad Between
Functional Foods and Pharma .... 723
References................................................... 724
potential and real functions as drugs leads are
succinctly reviewed and particularly exemplified.
An important aspect of this chapter is the analysis of marine natural products in relation to
new paradigms and particularities of other disciplines, such as genomics, combinatorial chemistry,
biosynthesis, and functional foods.