Current Medicinal Chemistry - Anti-Infective Agents, Vol. 3, No. 3, 2004
Contents
Marine
Natural Products
Guest
Editor: Raymond Andersen
Mining Marine Microorganisms as a
Source of New Antimicrobials and Antifungals Pp.181-195
V.S Bernan, M. Greenstein and G.T. Carter
Antifungal Compounds from Marine
Organisms Pp.197-220
Tadeusz F. Molinski
Inhibitors of Mycothiol-S-Conjugate
Amidase and Related Genes
Pp.221-231
G.M. Nicholas and C.A. Bewley
Antiviral Marine Natural Products Pp.233-249
Kirk R. Gustafson, Naoya Oku, and Dennis J. Milanowski
Abstracts
[Back
to top] Mining Marine Microorganisms as a
Source of New Antimicrobials and Antifungals
V.S Bernan, M. Greenstein and G.T. Carter
The oceans with their diverse life forms cover greater than 70% of the earth’s surface and present themselves as an unexplored area of opportunity. Owing to the many habitats in the sea, marine microorganisms encompass a complex and diverse assemblage of microscopic life forms, of which only 1% have been cultured or identified. Although just initiated in the past decade, natural products drug discovery from marine microorganisms has been encouraging. The chemical and biosynthetic diversity of these microbial compounds, coupled with their pharmacological activities, harbors great potential for the discovery of new antibiotics to combat the evolving resistance of pathogens to existing drugs. In this review, we summarize the diverse compounds identified from marine microorganisms and their potential as new antibacterial and antifungal drugs.
[Back
to top] Antifungal Compounds from Marine
Organisms
Tadeusz F. Molinski
Investigations into natural products from marine organisms have generated an enormous database of antibiotics of diverse chemical structures. Marine natural products almost certainly play key roles in the health of the host organism, and contribute to the dynamics of microbial communities within reef-dwelling organisms, but they have also provided a valuable library for screening for antifungal compounds effective against pathogens from the genera Candida, Aspergillus and Cryptococcus among others. This review covers antifungal compounds from marine invertebrates. The intention is to convey to the reader the ‘lay of the land’ with respect to structural chemotypes produced by marine organisms from the IndoPacific and Atlantic oceans that are most frequently encountered during cell-based screening programs for antifungal compounds. The sections cover marine macrolides, aminoalcohols and related heterocyclic structures, including oxazoles and other alkaloids, peptides as well as a few representative terpenoids and polyketides. Knowledge gained from the investigations of marine antifungal compounds may find use in directed synthesis of useful analogs and the further development of leads for the discovery of novel targets for intervention in fungal antibiosis.
[Back
to top] Inhibitors of Mycothiol-S-Conjugate
Amidase and Related Genes
G.M. Nicholas and C.A. Bewley
Mycothiol is a small molecular weight thiol exclusive to actinomycetes, a subgroup of Gram-positive bacteria. Mycothiol is composed of one unit each of 1-D-glucosamine, 1-D-myo-inositol and N-acetyl cysteine. Novel enzymes involved in mycothiol biosynthesis, mycothiol-mediated detoxification, and mycothiol reduction have recently been identified, and several of these share little or no sequence homology to known mammalian enzymes. Together, these points suggest that targeting of mycothiol-associated biochemistry may be a valid approach to identifying new types of antibiotics specific to actinomycetes, which include the medically important mycobacteria. This review discusses mycothiol literature to date, with emphasis on chemical approaches to identifying and synthesizing inhibitors and chemical probes to study mycothiol biochemistry.
[Back to
top] Antiviral
Marine Natural Products
Kirk R. Gustafson, Naoya Oku, and Dennis J. Milanowski
Limitations in our current antiviral treatment options and the continuing emergence of new pathogenic viruses have contributed to a growing need for new and effective chemotherapeutic agents to treat viral diseases. The marine environment provides a rich source of chemical diversity for the screening and identification of new compounds with desirable antiviral properties. Many of the new and structurally distinct metabolites that have been found in marine algae, invertebrate animals, and microorganisms have pronounced biological activities. Antiviral testing has revealed numerous compounds from structural classes including terpenoids, steroids, fatty acid derivatives, alkaloids, and peptides that potently inhibit both RNA and DNA viruses. Much of the recent antiviral research has focused on the human immunodeficiency virus (HIV) and the enzymes specific to this virus. Regardless of the specific assay system or screening approach that has been employed, a large number of structurally unique antiviral compounds from a broad taxonomic distribution of marine organisms have been identified. It is clear that marine natural products constitute a valuable chemical resource for the discovery of lead compounds that may aid in the development of new antiviral therapies.