Sesquiterpenoids from the Endophytic Fungus Rhinocladiella similis

Abstract

Ten new sesquiterpenoid derivatives, rhinomilisins A−J (1−10), along with six known analogues (11−16), were isolated from the mangrove-derived endophytic fungus Rhinocladiella similis. The structures of the new compounds were elucidated by their NMR and MS data, while the absolute configuration of 3 and 6 was determined by X-ray crystallographic analysis and Mosher's method, respectively. All isolated compounds (1−16) were evaluated for their cytotoxicity against the mouse lymphoma cell line L5178Y, and compounds 1, 7, and 15 showed moderate activity with IC 50 values of 5.0, 8.7, and 24.4 μM, respectively.

Trichodermaloids A–C, Cadinane Sesquiterpenes from a Marine Sponge Symbiotic Trichoderma sp. SM16 Fungus

“…This assignment was identical with the data in the literature. [10] The HR-MS and NMR data analyses showed that compound 4 shared the same planar structure of rhinomilisin E. [6] Liu et al reported the determination of the planar structure and relative configurations of this compound, however, its absolute configuration still remained unresolved. With this current work, we determined the absolute configurations of the four chiral centers in 4 as (1R,6S,7R,10S) by comparison the experimental with the calculated ECD spectra (Figure 4).…”

“…Compound 6 was identified as rhinomilisin G by compairing the MS and NMR data with the literature. [6] However, the absolute configuration of rhinomilisin G remained undetermined. Once the relative configuration of 6 was revealed as the same of rhinomilisin G by detailed analysis of the ROESY data (Figure 3), we measured the ECD spectrum for 6 in MeCN.…”

“…Subsequently, the cytotoxicity of 1 -6 was evaluated on three human cancer cell lines, NCIH-460 lung, NCI-H929 myeloma, and SW620 colorectal cancer cell lines, using MTT method (Table 3). Trichodermaloids A (1), B (2), and C (5) showed moderate cytotoxicities against the three cancer cell lines with IC 50 values at the range of 6.8 -12.7 μM, which were more potent than those of aspergilloid G (3), rhinomilisin E (4), and rhinomilisin G (6). The results implied the sesquiterpenes with two carboxylic acid groups (1, 2, and 5) were more active than those possessing one carboxylic acid group (3, 4, and 6).…”

“…Sesquiterpene is a huge family of biologically active natural products that have discovered from plants, [3] marine invertebrates, [4] and microbes. [5] A number of fungal sesquiterpenes have been discovered in recent years, which showed a wide spectrum of biological activities, such as anticancer, [6] antibacterial, [7] antifungal, [5] and so on. In recent years, marine sponge associated fungi have become an important source for sesquiterpene discovery.…”

“…The AcOEt extract of the fungus displayed characteristic LC-DAD profiles for sesquiterpenes. Subsequent large-scale fermentation and detailed chromatographic fractionation led to the discovery of six cadinane sesquiterpenes, including three new ones, trichodermaloids A (1), B (2), and C (5), and three known ones, aspergilloid G (3), rhinomilisin E (4), and rhinomilisin G (6), as shown in Figure 1. Combined analysis of the 13 C-NMR and HSQC spectra of 1 exhibited 15 carbon resonances, which was attributed to two methyl groups at δ(C) 21.0 and 17.1, two aliphatic methylene groups at δ(C) 19.8 and 24.2, two aromatic methines at δ(C) 111.8 and 119.6, three aliphatic methines at δ(C) 30.3, 39.2, and 43.0, four aromatic non-protonated carbons at δ(C) 128.0, 155.4, 129.0, and 141.5, and two carbonyl groups at δ(C) 175.4 and 167.7.…”