Andrastone A From the Deep-Sea-Derived Fungus Penicillium allii-sativi Acts as an Inducer of Caspase and RXRα-Dependent Apoptosis

Abstract

Two new (1, 2) and one known (3) meroterpenoids were isolated from the deep-sea-derived fungus Penicillium allii-sativi. The relative structures of new compounds were determined on the basis of an extensive analysis of the NMR and MS data, and the absolute configurations were established by ECD calculations. Andrastone A (1) is a rare andrastin bearing an unusual cyclopentan-1,3-dione. It shows a selectively antiproliferative effect against HepG2 tumor cells with an IC50 value of 7.8 μM. Mechanism study showed that apoptosis via Caspase and RXRα pathways are responsible for the inhibitory effect.

Bioactive Metabolites from the Mariana Trench Sediment-Derived Fungus Penicillium sp. SY2107

“…The 13 C and 1 H NMR data of 2-16 were reported in Tables S2-S7. Andrastone B (2) is a meroterpenoid recently isolated from a deep-sea-derived fungus Penicillium allii-sativi [22,23] and its crystal structure ( Figure 2) [Cu Kα radiation, Flack/Hooft parameter: −0.01(11)/0.08 (10)] was reported in this study for the first time. (Table 1).…”

“…Based on their high-resolution electrospray ionization mass spectroscopy (HRESIMS) data, extensive NMR spectroscopic analyses, and a single crystal X-ray diffraction as well as the comparison to the reported data, isolate 1 was elucidated as new meroterpenoid and 2-16 were identified as known compounds: andrastone B (16-epi-citreohybriddione A, 2) [22,23], (Z)-N-(4-hydroxystyryl)formamide (3) [24,25], pyripyropene A (4) [26], fumiquinazoline C (5) [27], spirotryprostatin C (6) [28], fumiquinazoline J (7) [29], pseurotin A (8) [30], penicilliumin B (9) [31], (-)-viridin (10) [32], monascusone A (11) [33], aspergillumarin A (12) [34], 1,2-seco-trypacidin (13) [35], di-Me 2,3'-dimethylosoate (14) [36], 2S-(2-hydroxypropanamido) benzamide (15) [37], and bisdethiobis (methylthio)gliotoxin (16) [38]. The 13 C and 1 H NMR data of 2-16 were reported in Tables S2-S7.…”

Antiproliferative Sorbicillinoids From the Deep-Sea-Derived Penicillium allii-sativi

“…Penicillium allii-sativi was isolated from the western Pacific Ocean (−4,302 m). The identification and fermentation of the fungus were reported previously ( Xie et al, 2019b ). As a result, a defatted extract (60.4 g) was obtained, which was subjected to CC over silica gel with gradient CH 2 Cl 2 -MeOH to get eight fractions (Fr.1–Fr.8).…”

“…During our ongoing search for structurally novel and biologically interesting secondary metabolites from deep-sea-derived microorganisms ( Yang et al, 2013 ; Niu et al, 2017 , 2020 ; Xie et al, 2019a ), the rice static fermentation extract of Penicillium allii-sativi MCCC 3A00580 exhibited potent in vitro antitumor activity. Previously, three meroterpenoids were obtained and andrastones A showed significant inhibitory effect against HepG2 tumor cells by activating caspase-3 and regulating the transcriptional activation function of RXR α ( Xie et al, 2019b ). Further investigation on this strain led to the discovery of two new and three known sorbicillinoid derivates ( Figure 1 ).…”

New Andrastin-Type Meroterpenoids from the Marine-Derived Fungus Penicillium sp.

“…The andrastin-type meroterpenoids derived from 5-dimethylorsellinic acid (DMOA) and farnesyl diphosphate (FPP) via a mixed polyketide-terpenoid pathway are characterized by a five-methyl substituted ent-5 α ,14 β -androstane skeleton (6,6,6,5-tetracarbocyclic skeleton) [ 3 , 4 ]. Since citreohybridones A and B were isolated in 1991, over 30 analogues have been isolated and characterized [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ]. Many andrastin-type meroterpenoids have shown potent cyotoxic, antifeedant, and insecticidal activities [ 4 , 8 , 10 ].…”