Cytotoxic Constituents of Aspergillus terreus from the Rhizosphere of Opuntia versicolor of the Sonoran Desert

Abstract

A novel cyclopentenedione, asterredione (1), two new terrecyclic acid A derivatives, (+)-5(6)-dihydro-6-methoxyterrecyclic acid A (2) and (+)-5(6)-dihydro-6-hydroxyterrecyclic acid A (3), and five known compounds, (+)-terrecyclic acid A (4), (-)-quadrone (5), betulinan A (6), asterriquinone D (7), and asterriquinone C-1 (8), were isolated from Aspergillus terreus occurring in the rhizosphere of Opuntia versicolor, using bioassay-guided fractionation. Acid-catalyzed reaction of 2 under mild conditions afforded 4, whereas under harsh conditions 2 yielded 5 and (-)-isoquadrone (9). Catalytic hydrogenation and methylation of 4 afforded 5(6)-dihydro-terrecyclic acid A (10) and (+)-terrecyclic acid A methyl ester (11), respectively. The structures of 1-11 were elucidated by spectroscopic methods. All compounds were evaluated for cytotoxicity in a panel of three sentinel cancer cell lines, NCI-H460 (non-small cell lung cancer), MCF-7 (breast cancer), and SF-268 (CNS glioma), and were found to be moderately active. Cell cycle analysis of 2, 4, and 5 using the NCI-H460 cell line indicated that 4 is capable of disrupting the cell cycle through an apparent arrest to progression at the G(1) and G(2)/M phases in this p53 competent cell line. A pathway for the biosynthetic origin of asterredione (1) from asterriquinone D (7) is proposed.

Natural Products from Plant-Associated Microorganisms: Distribution, Structural Diversity, Bioactivity, and Implications of Their Occurrence

“…84 Our pioneering work on nine strains of Sonoran desert plant-associated rhizosphere fungi has thus far resulted in the characterization of 41 metabolites of which 18 are new natural products. [85][86][87][88][89][90] Presented in Table 2 are the rhizosphere microorganisms investigated, their host plants, culture conditions employed for isolation of secondary metabolites, natural products encountered, and their biological activities.…”

Butyrolactone and Cycloheptanetrione from Mangrove-Associated Fungus <i>Aspergillus terreus</i>

“…1) Some different types of metabolites have been subsequently isolated from A. terreus strains. [2][3][4][5][6][7][8] Among these, some sesquiterpene lactone and butyrolactone compounds have exhibited potent acetylcholinesterase inhibition activity and cyclin-dependent kinases inhibition activity. 4,7) In our continuing search for new anti-tumor compounds from marine fungi, A. terreus was isolated from mangrove-associated marine sediments collected in Guangxi Zhuang Autonomous Region of China.…”

Endophytic fungi associated withTaxus fuana(West Himalayan Yew) of Pakistan: potential bio-resources for cancer chemopreventive agents

“…Based on such a targeted approach, NFjB inhibition is a plausible mechanism for the treatment or prevention of cancer (Schupp et al 2009;Luqman & Pezzuto 2010). Some fungal metabolites reported for potential to inhibit NFjB include trichodion, tricyclic acid, panepoxydone, hispidin derivatives, chaetoglobosin and mycoepoxydiene (Erkel 2000;Wijeratne et al 2003;Erkel et al 2007;Dou et al 2011;Wu et al 2011;Wang et al 2012). In our study, six of the isolates presented more than 60% NFjB inhibition, suggesting their potential to produce cancer chemopreventive compounds.…”