Trichodestruxins A–D: Cytotoxic Cyclodepsipeptides from the Endophytic Fungus Trichoderma harzianum

Abstract

Four new cyclodepsipeptides, trichodestruxins A–D (1–4), together with destruxin E2 chlorohydrin (5) and destruxin A2 (6), were isolated from the plant endophytic fungus Trichoderma harzianum by a bioassay-guided fractionation method. Their planar structures were elucidated on the basis of 1D and 2D NMR and MS/MS spectroscopic analyses. The stereochemical configuration was established by application of the advanced Marfey’s method, J-based configuration analysis, Mosher’s method, and chemical derivatizations. Trichodestruxin B contains hydroxy acid fragments of the THPA unit, while trichodestruxins A and C contain the β-methylproline moiety. All cyclodepsipeptides displayed cytotoxicity against HT-29, A549, and/or P388 cell lines with IC50 values of 0.7–19.1 μM.

Trichoderma: A Treasure House of Structurally Diverse Secondary Metabolites With Medicinal Importance

“…Bioassay-guided fractionation of the plant endophytic fungus T. harzianum KZ-20 afforded four new cyclodepsipeptides belonging to the destruxin family, i.e., trichodestruxins A-D (106-109), and two previously reported derivative, i.e., destruxin E2 chlorohydrin (110) and destruxin A2 (111) (Figure 5) (Liu Z. et al, 2020). Destruxins represent rare cyclic hexadepsipeptides.…”

“…93 showed selective cytotoxicity toward HeLa and MCF-7, with IC 50 s of 30.1 and 30.7 µM, respectively (Zhang et al, 2016). Cyclodepsipeptides 106-111 were active on HT-29, A549, and P388, with IC 50 s of 0.7-19.1 µM (Liu Z. et al, 2020). Cytochalasans 171 and 172 showed cytotoxicity on HeLa with IC 50 s of 5.72 and 27.4 µM, respectively, whereas 169, 170, and 173-177 were inactive (IC 50 > 40.0 µM) (Ding et al, 2012b,c).…”

Bioactive PKS–NRPS Alkaloids from the Plant-Derived Endophytic Fungus Xylaria arbuscula

“…The cytotoxic activities of 1–11 against human lung cancer cells A549 and human hepatocellular carcinoma cells HepG2 were determined by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay [ 22 , 23 ] . The cells were cultured in RPMI-1640 containing 10% ( v / v ) fetal bovine serum (FBS) and 0.4% ( v / v ) penicillin–streptomycin solution (10,000 units/mL penicillin and 10,000 μg/mL streptomycin, 100×) at 37 °C under 5% CO 2 .…”

New Isoquinoline Alkaloids from Paraphaeosphaeria sporulosa F03, a Fungal Endophyte Isolated from Paepalanthus planifolius

“…Endophytic fungi are still regarded as an important source of new and structurally diverse natural products that are endowed with a wide range of bioactivities [1][2][3]. Isoquinoline alkaloids (IQAs) are a large class of secondary metabolites produced not only by plants, but also by animals and microorganisms.…”