Caspase-1 and -3 Inhibiting Drimane Sesquiterpenoids from the Extremophilic Fungus Penicillium solitum

Abstract

Two new drimane sesquiterpene lactones and one new tricarboxylic acid derivative were isolated from the Berkeley Pit extremophilic fungus Penicillium solitum. The structures of these compounds were deduced by spectroscopic analysis. Berkedrimanes A and B inhibited the signal transduction enzymes caspase-1 and caspase-3 and mitigated the production of interleukin 1-β in the induced THP-1 (promonocytic leukemia cell line) assay.

Chemical diversity from the Tibetan Plateau fungi Penicillium kongii and P. brasilianum

“…The endophytic fungi (Arunpanichlert et al 2010; Zhu et al 2015) and soil fungi (Tansakul et al 2014; Daengrot et al 2015) were the most studied fungi in this genus and a number of natural products have been reported to exhibit diverse activities including anti-inflammatory, cytotoxic (Xue et al 2014), or anti-hepatitis C virus (Kozlovskii et al 2013; Nishikori et al 2016). Other strains from extreme conditions also raised the great interest to mine novel structures, such as halotolerant or extremophilic strains (Lu et al 2008; Stierle et al 2012)，deep sea-derived strains (Li et al 2013), and marine animal-derived strains (Qi et al 2013). The resulted compounds cover different biological activities including cytotoxic activity against cancer cell lines (Li et al 2014; Zhang et al 2016), potent inhibitory activity against bacteria (Zheng et al 2016), antifungal activity (Daengrot et al 2015), inhibiting LPS-induced inflammation (Shin et al 2016), and inhibitory activity against protease (Sun et al 2014).…”

Purpurides B and C, Two New Sesquiterpene Esters from the Aciduric Fungus Penicillium purpurogenum JS03‐21

“…Their structures were elucidated by spectroscopic analysis, X-ray single-crystal diffraction, and application of Marfeys method. To the best of our knowledge, purpuride (4) reported in 1973 was the first natural product known to possess this skeleton [10], and the secondary example was the recently reported berkedrimanes A and B (3) from the extremophilic fungus P. solitum [11]. Compounds 1 and 2 showed moderate antimicrobial activities against Enterobacter aerogenes and Pseudomonas aeruginosa with MIC values in the range of 1.2 -2.6 mm.…”

“…In our continuing search for new and bioactive natural products of fungal origin from special niches [3] [4], we noted that the secondary metabolites of such microorganisms can be regulated by variation of the external pH [5] [6], and some silent genes could be activated at low [7] and high [8] external pH values. To the best of our knowledge, purpuride (4) reported in 1973 was the first natural product known to possess this skeleton [10], and the secondary example was the recently reported berkedrimanes A and B (3) from the extremophilic fungus P. solitum [11]. From the fermented filtrate of P. purpurogenum JS03-21 at pH 2, we identified six new polyketides with anti-H1N1 activity [9].…”

Bioactive Secondary Metabolites from Acid Mine Waste Extremophiles

“…The assembling inflammasome activates pro-caspase-1, which in turn activates (cleaves) pro-IL-1β and other proinflammatory cytokines [18]. Test compounds are administered to these induced THP-1 cells and the production of cytokines post-administration is determined [43, 49]. …”

“…These effects have been attributed to MWCNT length, diameter, aggregation state, contaminants, aspect ratio/rigidity, and release of reactive oxygen species [52]. The induced-inflammasome assay is a useful tool in assessing the direct inhibition of caspase-1 as a means of moderating inflammation in a cellular system and also provides lead compounds that could mitigate the direct toxicity of MWCNT [43, 49]. …”