Bioactive Cycloperoxides Isolated from the Puerto Rican Sponge Plakortis halichondrioides.
ABSTRACT Two new five-membered-ring polyketide endoperoxides, epiplakinic acid F methyl ester (1) and epiplakinidioic acid (3), and a peroxide-lactone, plakortolide J (2), were isolated from the Puerto Rican sponge Plakortis halichondrioides, along with two previously reported cyclic peroxides, 4 and 5. The structures of the new metabolites were determined by spectroscopic and chemical analyses. The absolute stereostructures of 1, 2, and 5 were determined by degradation reactions followed by application of Kishi's method for the assignment of absolute configuration of alcohols. Biological screening of cycloperoxides 1-5 and semisynthetic analogues 7-12 for cytotoxic activity against various human tumor cell lines revealed that compounds 3, 4, and 11 are very active. Upon assaying for antimalarial and antitubercular activity, some of the compounds tested showed strong activity against the pathogenic microbes Plasmodium falciparum and Mycobacterium tuberculosis.
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ABSTRACT: Currently, one third of the world's population is infected with Mycobacterium tuberculosis and 8.9-9.9 million new and relapse cases of tuberculosis are reported every year. The emergence of new cases, the increased incidence of multi-drug resistant strains of M. tuberculosis, and the adverse effects of first- and second-line antituberculosis drugs have led to renewed research interest in natural products in the hope of discovering new antitubercular leads. Interestingly, hundreds of natural products, possessing novel, uncommon, and known structural architectures, have been reported to exhibit activity towards non-resistant and multi-drug resistant strains of M. tuberculosis. The present review covers literature published during the last five years about those naturally occurring compounds with reported growth inhibitory activity in vitro towards sensitive and resistant M. tuberculosis strains. Compounds with antitubercular properties at minimal inhibitory concentrations (MICs) of less than 50 μg/mL or 60 μM were selected and grouped according to their source of origin (plants, bacteria, fungi, marine organisms, etc) and chemical type (terpenes, steroids, alkaloids, flavonoids, poliketides, peptides, etc). In some cases, the selection covers those structurally relevant natural products with low bioactivity (MICs of ≤128 μg/mL), and also those semisynthetic derivatives with remarkable antitubercular activity (MICs of ≤10 μg/mL). Additionally, this review includes a special section for those natural products that specifically target genes or enzymes of M. tuberculosis.European journal of medicinal chemistry 03/2012; 49:1-23. · 3.27 Impact Factor
Article: Antiplasmodial Natural Products[show abstract] [hide abstract]
ABSTRACT: Malaria is a human infectious disease that is caused by four species of Plasmodium. It is responsible for more than 1 million deaths per year. Natural products contain a great variety of chemical structures and have been screened for antiplasmodial activity as potential sources of new antimalarial drugs. This review highlights studies on natural products with antimalarial and antiplasmodial activity reported in the literature from January 2009 to November 2010. A total of 360 antiplasmodial natural products comprised of terpenes, including iridoids, sesquiterpenes, diterpenes, terpenoid benzoquinones, steroids, quassinoids, limonoids, curcubitacins, and lanostanes; flavonoids; alkaloids; peptides; phenylalkanoids; xanthones; naphthopyrones; polyketides, including halenaquinones, peroxides, polyacetylenes, and resorcylic acids; depsidones; benzophenones; macrolides; and miscellaneous compounds, including halogenated compounds and chromenes are listed in this review.Molecules. 01/2011;