Involucratusins A–H: Unusual Cadinane Dimers from Stahlianthus involucratus with Multidrug Resistance Reversal Activity

Abstract

Three novel cadinane dimers, involucratusins A–C (1–3), five unique nor-cadinane-dimers, involucratusins D–H (4–8), together with a known compound (9) were isolated from the rhizomes of Stahlianthus involucratus. Their challenging structures and absolute configurations were determined by spectroscopic data, CD experimentation, chemical conversions and single-crystal X-ray diffraction. Compounds 1–3 are unusual cadinane dimers with new connection and novel cores. Compound 4 is a unique nor-cadinane-dimer, and 5 and 6 are two pairs of hemiketal racemates with novel dinor-cadinane-dimer backbone. Compounds 7 and 8 represent unusual dodecanor-cadinane-dimer and tetradecanor-cadinane-dimer carbon skeletons, respectively. The possible biogenetic pathways of 1–8 were proposed, involving nucleophilic addition, SN2 nucleophilic displacement, [3 + 3] benzannulation, oxidative cleavage, decarboxylation, and oxidative phenol coupling reactions. Multidrug resistance (MDR) reversal activity assay of the isolates were evaluated in doxorubicin-resistant human breast cancer cells (MCF-7/DOX). The combined use of these novel cadinane dimers at a concentration of 10 μM increased the cytotoxicity of doxorubicin by 2.2–5.8-fold. It is the first report about the MDR reversal activity of cadinane dimers.

Developmental Transcriptional Enhancers: A Subtle Interplay between Accessibility and Activity

“…[41] While this per se does not indicate a causal link, Li and Arnosti [39] showed that overexpression of the repressor Knirps in D. melanogaster embryos led to the decrease of H4 acetylation at its target enhancers. [97] As lysine acetylation reduces nucleosome stability and increases accessibility of linker DNA, [98][99][100] differential action by co-activators and co-repressors at the enhancer could result in the observed quantitative differences between the active, primed, and repressed states. [15] Overall, in addition to the broad and local mechanisms seeding enhancer accessibility that were discussed in the previous section, accessibility of enhancers can be also fine-tuned during their operation, as a consequence of multiple regulatory events.…”

Bioassay-Guided Isolation and HPLC Quantification of Antiproliferative Metabolites from Stahlianthus thorelii

“…Curcumin is a major ingredient extracted from Curcuma species, which had the antiproliferative activity and was proved to induce apoptosis of Rb cells via inhibition of JAK/STAT pathway [9]. Stahlianthus thorelii and Stahlianthus invocratus are members of the Zingiberaceae famil and both are known as "Khuong tam that" used in Vietnamese and Chinese folk medicine, respectively, to treat inflammation, pneumonia, diarrhea, and anticancer [10][11][12]. However, there are seldom reports concerning chemical components and bioactivities related to diseases for Stahlianthus species except for limited studies on Stahlianthus invocratus about its chemical components [10,13], and the bioactivities of its ethanol extract [14].…”

“…Stahlianthus thorelii and Stahlianthus invocratus are members of the Zingiberaceae famil and both are known as "Khuong tam that" used in Vietnamese and Chinese folk medicine, respectively, to treat inflammation, pneumonia, diarrhea, and anticancer [10][11][12]. However, there are seldom reports concerning chemical components and bioactivities related to diseases for Stahlianthus species except for limited studies on Stahlianthus invocratus about its chemical components [10,13], and the bioactivities of its ethanol extract [14]. This study aimed to isolate bioactive compounds and elucidate their structures, based on antiproliferative-directed fractionations.…”

Seven new cytotoxic phenylspirodrimane derivatives from the endophytic fungus Stachybotrys chartarum

“…The dimers were also found to possess potential biological activities that were different to those of the monomers, such as antibacterial activities, HIV-1 protease inhibitory effects, and potential ET receptor antagonists. 10,11,15 Recently, during metabolite research into endophytic fungi from Pinellia ternata, [16][17][18][19] chemical investigation of the strain Stachybotrys chartarum PT2-12 led to the discovery of four phenylspirodrimane C-C-coupled dimers (1)(2)(3)(4) and three new monomers (5)(6)(7), along with four known examples (8)(9)(10)(11) (Fig. 1).…”