New Enantiomers of a Nor-Bisabolane Derivative and Two New Phthalides Produced by the Marine-Derived Fungus Penicillium chrysogenum LD-201810

Abstract

Marine-derived fungi are a treasure house for the discovery of structurally novel secondary metabolites with potential pharmaceutical value. In this study, a pair of new nor-bisabolane derivative enantiomers (±)−1 and two new phthalides (4 and 5), as well as four known metabolites, were isolated from the culture filtrate of the marine algal-derived endophytic fungus Penicillium chrysogenum LD-201810. Their structures were established by detailed interpretation of spectroscopic data (1D/2D NMR and ESI-MS). The optical resolution of compound (±)−1 by chiral HPLC successfully afforded individual enantiomers (+)−1 and (−)−1, and their absolute configurations were determined by TDDFT-ECD calculations. Compound (±)−1 represents the first example of bisabolane analogs with a methylsulfinyl substituent group, which is rare in natural products. All of the isolated compounds 1–7 were evaluated for their cytotoxic activity against A549, BT-549, HeLa, HepG2, MCF-7, and THP-1 cell lines, as well as for antifungal activity against four plant pathogenetic fungi (Alternaria solani, Botrytis cinerea, Fusarium oxysporum, and Valsa mali). Compound 2, a bisabolane-type sesquiterpenoid, was shown to possess excellent activity for control of B. cinerea with half-maximal inhibitory concentration (IC50) of 13.6 μg/mL, whereas the remaining investigated compounds showed either weak or no cytotoxic/antifungal activity in this study.

Polyketides isolated from an endophyte Penicillium oxalicum 2021CDF-3 inhibit pancreatic tumor growth

“…In addition, eight previously reported compounds ( 3 – 10 ) were also isolated from this fungus. They were finally characterized as 6,7-dihydroxy-3-methoxy-3-methylphthalide ( 3 ) ( Wang et al, 2013 ), chrysoalide B ( 4 ) ( Ge et al, 2021 ), rubralide C ( 5 ) ( Kimura et al, 2007 ), cis -(3 RS ,4 SR )-3,4-dihydro-3,4,8-trihydroxynaphthalen-1(2 H )-one ( 6 ) ( Couché et al, 2009 ), 2,5-dimethyl-7-hydroxychromone ( 7 ) ( Kashiwada et al, 1984 ), (7 R )-(hydroxy(phenyl)methyl)-4 H -pyran-4-one ( 8 ) ( Xu et al, 2019 ), 6-benzyl-4-oxo-1,4-dihydropyridine-3-carboxamide ( 9 ) ( Ye et al, 2005 ), and carbonarone A ( 10 ) ( Zhang et al, 2007 ), respectively, by comparison of their spectroscopic data with literatures.…”

Cytotoxic secondary metabolites isolated from Penicillium sp. YT2019-3321, an endophytic fungus derived from Lonicera Japonica

“…Compound 1 possessed the same planar structure as chrysoalide B, a new phthalide produced by the marine-derived fungus Penicillium chrysogenum LD-201810 ( Ge et al, 2021 ). Surprisingly, the specific rotation value of 1 was found to be zero.…”

Chemistry and Bioactivity of Marine-Derived Bisabolane Sesquiterpenoids: A Review

“…Compared to bisabolanes isolated from terrestrial fungi, some of bisabolanes from marine-derived fungi possess unique functionalities. For example, the sulfurated bisabolanes were exclusively isolated from marine fungi, including 25 with a rare methylsulfonyl group isolated from the deep sea sediment-derived fungus A. sydowii MCCC 3A00324 ( Niu et al, 2020 ), 40 and 42 – 43 incorporating with a rare methylsulfinyl group isolated from the marine algal-derived endophytic fungus P. chrysogenum LD-201810 ( Ge et al, 2021 ) and the seawater-derived fungus A. flavipes 297 ( Chen et al, 2021 ), respectively. 52 isolated from a marine red alga-epiphytic isolate of T. asperellum Y6−2, represented a rare example of nor-sesquiterpenes with a spiro system ( Shi et al, 2019 ).…”

“…Through chemical epigenetic manipulation strategy, the gorgonian-derived fungus A. versicolor XS-20090066 was found to produce a new bisabolane aspergillusene E ( 39 ) with a benzofuran moiety, by the addition of histone deacetylase inhibitor, suberoylanilide hydroxamic acid, and DNA methyltransferase inhibitor, 5-azacytidine ( Wu et al, 2020 ). A pair of new S-containing norbisabolane enantiomers methylsulfinyl-1-hydroxyboivinianin A [(±)- 40 ] were produced by the marine algal-derived endophytic fungus P. chrysogenum LD-201810 ( Ge et al, 2021 ). 40 was proven to possess a rare methylsulfinyl substituent, and finally afforded individual enantiomers (+)- 40 and (−)- 40 by chiral HPLC.…”

“…These compounds incorporate an eight continuous carbons side chain, which cause high structural diversity to generate abundant functionalities including double bond, lactone, furan, pyran, and so on, by oxidation, reduction, esterification, and cyclization ( Niu et al, 2020 ; Chen et al, 2021 ). Moreover, some unique members, such as norbisabolanes ( Jian Li et al, 2015 ; Ge et al, 2021 ), dimers ( Sun et al, 2012 ; Georgantea et al, 2013 ), glycosides ( Lv et al, 2014 ), adducts ( Xiao-Dong Li et al, 2015 ), have also been characterized. Chemically speaking, the findings of these fascinating molecules provide considerable chemical foundation in the course of new drugs and agricultural chemicals discovery.…”