Marine-Deriv
759
Part F | 32.1
32. Marine-Derived Fungal Metabolites
Sherif S. Ebada, Peter Proksch
Marine-derived metabolites continue to be a prolific source for bioactive natural products with
a high tendency to become drug candidates.
Recently, eribulin mesylate (E7389), a synthetic
derivative of halichondrin B, was approved by the
US FDA (Food and Drug Administration) for the
treatment of breast cancer metastases, going under
the trade name Halaven. Some other marine-derived pharmaceuticals have likewise already been
approved and launched onto the market, including
Yondelis (trabectedin), Prialt (ziconotide), Retrovir
(zidovudine), Cytosar (cytarabine, Ara-C), and ViraA (vidarabine, Ara-A). Research interests in marine
natural products have increased in the last few
decades, in particular with respect to compounds
isolated from marine-derived fungi. In this chapter, a historical background of marine-derived
pharmaceuticals and fungal metabolites will be
presented, including potential classes of bioactive
chemical compounds. In addition, a perspective
on the sustainability of marine-derived fungi with
regard to a continuous supply of bioactive compounds for market needs rather than a pursuit of
32.1 Overview ............................................. 759
32.2 Drug Screening from Marine Organisms 760
32.2.1 US FDA-Approved
Marine-Inspired Pharmaceuticals 760
32.2.2 Marine Pharmaceuticals
in Phase III Clinical Trials............ 761
32.2.3 Marine Pharmaceuticals
in Phase II Clinical Trials............. 762
32.2.4 Marine Pharmaceuticals
in Phase I Clinical Trials.............. 763
32.2.5 Marine Pharmaceuticals
in the Preclinical Phase.............. 764
32.3 Marine Organic Compounds.................. 765
32.3.1 Alkaloids .................................. 765
32.3.2 Diketopiperazines...................... 769
32.3.3 Polyketides ............................... 770
32.3.4 Terpenes................................... 777
32.3.5 Marine Peptides and Proteins..... 781
32.4 Conclusions ......................................... 782
References................................................... 782
other strategies such as aquafarming will be
discussed.
32.1 Overview
Natural products continue to be a gold mine of lead
structures for pharmaceuticals used for the treatment of
various human diseases. More than two-thirds of active
drug ingredients are either natural products or derivatives thereof [32.1]. In spite of the great advances in
medicine that have been achieved, there are still no
cures for some of the most deadly and crippling ailments, such as AIDS, several types of cancer, and many
viral and fungal diseases. In addition, the emergence
of resistant strains of previously curable illnesses, e.g.,
strains of tuberculosis, malaria, and the Ebola virus towards standard drug therapy has made new therapeutic
regimens necessary as much as ever to save and improve human lives.
Marine ecosystems, occupying about 70% of the
planet’s surface area, represent an unexploited source
of potential pharmaceuticals. These compounds have
proved to be a pipeline of secondary metabolites featuring unprecedented chemical scaffolds and unique
pharmacological properties which have encouraged natural product chemists during the last 60 years to
explore marine organisms [32.2, 3]. Several marine
natural products have succeeded in reaching the pharmaceutical market or are in clinical trials for the
treatment of serious human disorders ranging from
severe pain and microbial infections to immune diseases and cancer [32.4]. Moreover, a huge number of marine natural products have been reported
759
Part F | 32.1
32. Marine-Derived Fungal Metabolites
Sherif S. Ebada, Peter Proksch
Marine-derived metabolites continue to be a prolific source for bioactive natural products with
a high tendency to become drug candidates.
Recently, eribulin mesylate (E7389), a synthetic
derivative of halichondrin B, was approved by the
US FDA (Food and Drug Administration) for the
treatment of breast cancer metastases, going under
the trade name Halaven. Some other marine-derived pharmaceuticals have likewise already been
approved and launched onto the market, including
Yondelis (trabectedin), Prialt (ziconotide), Retrovir
(zidovudine), Cytosar (cytarabine, Ara-C), and ViraA (vidarabine, Ara-A). Research interests in marine
natural products have increased in the last few
decades, in particular with respect to compounds
isolated from marine-derived fungi. In this chapter, a historical background of marine-derived
pharmaceuticals and fungal metabolites will be
presented, including potential classes of bioactive
chemical compounds. In addition, a perspective
on the sustainability of marine-derived fungi with
regard to a continuous supply of bioactive compounds for market needs rather than a pursuit of
32.1 Overview ............................................. 759
32.2 Drug Screening from Marine Organisms 760
32.2.1 US FDA-Approved
Marine-Inspired Pharmaceuticals 760
32.2.2 Marine Pharmaceuticals
in Phase III Clinical Trials............ 761
32.2.3 Marine Pharmaceuticals
in Phase II Clinical Trials............. 762
32.2.4 Marine Pharmaceuticals
in Phase I Clinical Trials.............. 763
32.2.5 Marine Pharmaceuticals
in the Preclinical Phase.............. 764
32.3 Marine Organic Compounds.................. 765
32.3.1 Alkaloids .................................. 765
32.3.2 Diketopiperazines...................... 769
32.3.3 Polyketides ............................... 770
32.3.4 Terpenes................................... 777
32.3.5 Marine Peptides and Proteins..... 781
32.4 Conclusions ......................................... 782
References................................................... 782
other strategies such as aquafarming will be
discussed.
32.1 Overview
Natural products continue to be a gold mine of lead
structures for pharmaceuticals used for the treatment of
various human diseases. More than two-thirds of active
drug ingredients are either natural products or derivatives thereof [32.1]. In spite of the great advances in
medicine that have been achieved, there are still no
cures for some of the most deadly and crippling ailments, such as AIDS, several types of cancer, and many
viral and fungal diseases. In addition, the emergence
of resistant strains of previously curable illnesses, e.g.,
strains of tuberculosis, malaria, and the Ebola virus towards standard drug therapy has made new therapeutic
regimens necessary as much as ever to save and improve human lives.
Marine ecosystems, occupying about 70% of the
planet’s surface area, represent an unexploited source
of potential pharmaceuticals. These compounds have
proved to be a pipeline of secondary metabolites featuring unprecedented chemical scaffolds and unique
pharmacological properties which have encouraged natural product chemists during the last 60 years to
explore marine organisms [32.2, 3]. Several marine
natural products have succeeded in reaching the pharmaceutical market or are in clinical trials for the
treatment of serious human disorders ranging from
severe pain and microbial infections to immune diseases and cancer [32.4]. Moreover, a huge number of marine natural products have been reported