ABSTRACT
Cancer accounted for huge number of deaths, which represents about 13% of all deaths worldwide, and the number of the deaths due to cancer is increasing. Natural products and their synthetic analogs are widely used as antitumor drugs. As represented by these drugs, many anticancer drugs originated from cytotoxic compounds. Marine natural products are a gold mine of strong bioactive compounds with unique structures created in evolution of organisms over hundred million years. However, in the field of drug discovery, most studies have focused on plant essences and bacterial metabolites, and candidate compounds from marine origin are still remaining relatively unexplored.
Subject(s)
Antineoplastic Agents/metabolism , Aquatic Organisms/metabolism , Drug Discovery , Marine Toxins/biosynthesis , Animals , Anthozoa/metabolism , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Cyanobacteria/metabolism , Cyclopropanes/chemistry , Cyclopropanes/metabolism , Cyclopropanes/pharmacology , Cyclopropanes/therapeutic use , Humans , Macrolides/chemistry , Macrolides/metabolism , Macrolides/pharmacology , Macrolides/therapeutic use , Marine Toxins/chemistry , Marine Toxins/pharmacology , Marine Toxins/therapeutic use , Peptides, Cyclic/biosynthesis , Peptides, Cyclic/chemistry , Peptides, Cyclic/pharmacology , Peptides, Cyclic/therapeutic use , Porifera/metabolismABSTRACT
Novel sesquiterpene alkaloids, halichonines A (1), B (2), and C (3), were identified from the marine sponge Halichondria okadai Kadota. By spectroscopic analyses and synthesis, their structures were revealed to include a 6,6-bicyclic ring system and two prenylated amine moieties. In addition, 2 induced apoptosis in HL60 human leukemia cells.
Subject(s)
Alkaloids/chemistry , Alkaloids/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Porifera/chemistry , Sesquiterpenes/chemistry , Sesquiterpenes/pharmacology , Alkaloids/isolation & purification , Animals , Antineoplastic Agents/isolation & purification , HL-60 Cells , Humans , Inhibitory Concentration 50 , Models, Molecular , Molecular Conformation , Sesquiterpenes/isolation & purificationABSTRACT
The EtOH extract of tarragon Artemisia dracunculus, a perennial herb in the family Asteraceae, was found to potently inhibit α-melanocyte-stimulating hormone (α-MSH) induced melanin production in B16 mouse melanoma cells. Bioassay-guided fractionation led to the isolation of two alkamide compounds, isobutyl (1) and piperidiyl (2) amides of undeca-2E,4E-dien-8,10-dynoic acid. The respective EC(50) values for melanin biosynthesis inhibition were 1.8 and 2.3 µg/mL for 1 and 2.
Subject(s)
Artemisia/chemistry , Melanins/antagonists & inhibitors , Melanoma, Experimental/drug therapy , Plant Extracts/pharmacology , Polyunsaturated Alkamides , Skin Neoplasms/drug therapy , alpha-MSH/antagonists & inhibitors , Animals , Cell Survival/drug effects , Humans , Inhibitory Concentration 50 , Magnetic Resonance Spectroscopy , Melanins/biosynthesis , Melanoma, Experimental/pathology , Mice , Plant Extracts/chemistry , Polyunsaturated Alkamides/chemistry , Polyunsaturated Alkamides/isolation & purification , Polyunsaturated Alkamides/pharmacology , Skin Neoplasms/pathology , Tumor Cells, Cultured , alpha-MSH/metabolismABSTRACT
Pinnarine (1), a new macrocyclic alkaloid, was isolated from the black marine sponge Halichondria okadai. The structure was elucidated on the basis of 2D NMR and comparison with the spectra of the co-isolated known halichlorine. Further confirmation of the structure and the absolute configuration was validated by a synthetic method from authentic pinnaic acid and CD analysis. The isolation of pinnarine also suggested a biogenetic pathway from pinnaic acid to halichlorine.
