Biologically Active Tetranorditerpenoids from the Fungus Sclerotinia homoeocarpa Causal Agent of Dollar Spot in Turfgrass

Abstract

Nine new tetranorditerpenoid dilactones (2-10), together with two previously reported norditerpenoids dilactones (1, 11), and two known putative biosynthetic intermediates oidiolactone-E (12) and 13 were isolated from an ethyl acetate extract of a culture medium of Sclerotinia homoeocarpa. Structures and absolute configuration of these compounds were determined by spectroscopic methods and confirmed by X-ray crystallographic analysis of representative compounds. Compounds were evaluated for herbicidal, antiplasmodial and cytotoxic activities. Compounds 1, 2, 6, 7, 11 were more active as growth inhibitors in a duckweed bioassay (I 50 values of 0.39 -0.95 µM) than more than half of 26 commercial herbicides previously evaluated using the same bioassay. Some of these compounds exhibited strong antiplasmodial activities as well, but they also had cytotoxic activity thus precluding them as potential antimalarial agents.Malaria continues to be a major cause of morbidity and mortality in many parts of the tropics and subtropics. Every year about 500 million people become ill with malaria and over a million people, most of them young children, die of this disease. 1 Wide-spread resistance to first-line antimalarial drugs has hampered the effective control of this disease. Many efforts are underway to develop new classes of antimalarials to counter this trend. 2 One of these involves searching for compounds to inhibit unique metabolic pathways in the apicoplast. 2,3 Plasmodium parasites, which cause malaria in humans, contain an organelle called the apicoplast. 4 The apicoplast is very similar to plastids (chloroplasts are one of several plastid forms) of plants and is believed to have been acquired by the engulfment of an ancestral alga and retention of the algal plastid. The apicoplast is essential for the survival of parasites, and it contains many plant-like metabolic pathways such as essential amino acid, heme, and type *To whom correspondence should be addressed. Tel.: 1-662-915-1019. Fax: 1-662-915-1006. dhammika@olemiss.edu . NIH Public AccessAuthor Manuscript J Nat Prod. Author manuscript; available in PMC 2010 December 1. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptII fatty acid biosynthesis not present in the vertebrate hosts of malaria parasites. 4 Several studies have been initiated to evaluate antimalarial activity of herbicides and natural phytotoxins which are known to inhibit metabolic pathways of the plastid in plants. 5 -7 A number of plant pathogenic fungi are known to release phytotoxins that disrupt biological processes in plants. [8][9][10] Some of these have also been shown to inhibit metabolic pathways in the plastid; 11 thus, plant pathogens could be a potential source of antimalarial compounds.As part of a program to search for antimalarial compounds from natural sources, we initiated a project to screen phytopathogenic fungi for antimalarial activity. Sclerotinia homoeocarpa is the causal agent of "dollar spot," the most prevalent disease of turfgrass in...

RNA-Seq Analysis of the Sclerotinia homoeocarpa – Creeping Bentgrass Pathosystem

“…Early studies noted root browning and cell death through the production of diffusible toxins [12] . Recent studies have identified several tetranorditerpenoid compounds that could be responsible for the root-browning and exhibit extremely phytotoxic properties; however, a correlation between the production of these compounds and disease symptoms was not established [13] .…”

Mechanisms of Environmental Stress Tolerance in Turfgrass

“…The application of chemical agents is a common method to avoid biotic-stress-induced damage in turfgrass. For instance, dollar spot disease in turfgrass is caused by the fungus Clarireedia homoeocarpa, and it could be suppressed by fungicide in creeping bentgrass [199][200][201][202]. Captan and Chlorothalonil are efficient fungicides against Curvularia trifolii, which causes foliar yellowing of Paspalum vaginatum [5,194].…”

Marine natural products

“…192 Examination of the endophytic A. wentii EN-48 (brown alga Sargassum sp., source unspecied) revealed three new tetranorlabdane diterpenoids asperolide A-C 203-205 193 in addition to the terrestrial fungal metabolites, wentilactones A and B, 194 LL-Z1271-b, 195 and a known tetranorditerpenoid derivative. 196 All of these known metabolites were rst time marine isolates. 193 Application of OSMAC (one strain-many compounds) methodology to Asteromyces cruciatus (unidentied decaying green alga, La Jolla, USA) identied the pentapeptide lajollamide A 206 (absolute conguration determined by total synthesis).…”