AS1041, a novel derivative of marine natural compound Aspergiolide A, induces senescence of leukemia cells via oxidative stress-induced DNA damage and BCR-ABL degradation.

Chronic myelogenous leukemia (CML) is characterized by the constitutive activation of BCR-ABL tyrosine kinase. Imatinib was approved for CML therapy, however, BCR-ABL-dependent drug resistance, especially BCR-ABL-T315I mutation, restricts its clinical application. In this study, we reported anthraquinone lactone AS1041, a synthesized derivative of marine natural compound Aspergiolide A, showed anti-leukemia effect in vitro and in vivo by promoting cell senescence.

Nonenzymatic Self-Assembly Access to Diverse -Quinone Methide-Based Pseudonatural Products.

A nonenzymatic self-assembly program was introduced to explore diverse clavatol-based pseudonatural products (PNPs) in a marine-derived fungus. Intermolecular couplings of the chemoreactive -quinone methide of clavatol with native acceptors led to 14 clavatol-based PNPs with five categories, and compounds , , -, and are new. In particular, and possessed an unprecedented oxa-angular tetracyclic scaffold with highly oxidized modification and exhibited cytotoxicity.

Linear polyketides produced by co-culture of and .

Unlabelled: Two new polyketides, penifellutins A () and B (), possessing a 22 carbon linear skeleton, were isolated from a co-culture of the deep-sea-derived fungi PRB-2 and HDN14-323. Meanwhile, two esterification products of , penifellutins C () and D (), were obtained because compound could be esterified spontaneously when stored in methanol. Their configurations were difficult to determine because of chiral central crowdedness, structural flexibility and instability.

Pyrazinopyrimidine alkaloids from a mangrove-derived fungus Aspergillus versicolor HDN11-84.

Pyrazinopyrimidine-type alkaloids bearing a pyrazino[1,2-a] pyrimidine moiety, often have different functional groups substituted at C-8' or C-2'/C-8', generally further forming unique spiro-/conjugated ring systems. Four undescribed pyrazinopyrimidine-type alkaloids, including three natural products pyrasplorines A-C and an artifact deg-pyrasplorine B, as well as a biogenetically related versicoloid A were discovered from the extract of a mangrove-derived fungus Apergillus verisicolor HDN11-84. Pyrasplorine A contains unique spiral-type skeleton (composed of cyclopentenone ring with the pyrazino[1,2-a] pyrimidine core) which is unprecedented in pyrazinopyrimidine-type alkaloids.

Polyhydroxy -Terphenyls from a Mangrove Endophytic Fungus LDJ-5.

Six undescribed polyhydroxy -terphenyls, namely asperterphenyllins A-F, were isolated from an endophytic fungus LDJ-5. Their structures were determined by NMR and MS data. Differing from the previously reported -terphenyls, asperterphenyllin A represents the first -terphenyl dimer connected by a C-C bond.

Ascandinines A-D, Indole Diterpenoids, from the Sponge-Derived Fungus HDN15-152.

Four new indole diterpenoids, ascandinines A-D (-), were isolated from an Antarctic sponge-derived fungus HDN15-152. Their structures, including absolute configurations, were established based on NMR data, computational calculations, and biosynthetic considerations. Ascandinine A () possesses an unprecedented 2-oxabicyclo[2.

Staprexanthones, Xanthone-Type Stimulators of Pancreatic β-Cell Proliferation from a Mangrove Endophytic Fungus.

This project was focused on the discovery of novel compounds that promote endogenous β-cell regeneration. Screening of extracts identified the fungus as a promising candidate. After fermentation and extraction of , we isolated five new prenylated xanthones, namely, staprexanthones A-E (-), with staprexanthone A () being the first natural xanthone bearing a rare 4,5-dimethyl-1,3-dioxolane moiety.

Fungal mycotoxin penisuloxazin A, a novel C-terminal Hsp90 inhibitor and characteristics of its analogues on Hsp90 function related to binding sites.

Hsp90 is a promising drug target for cancer therapy. However, toxicity and moderate effect are limitations of current inhibitors owing to broad protein degradation. The fungal mycotoxin penisuloxazin A (PNSA) belongs to a new epipolythiodiketopiperazines (ETPs) possessing a rare 3H-spiro[benzofuran-2,2'-piperazine] ring system.

Dimeric Tetrahydroanthracene Regioisomers and Their Monomeric Precursor Produced by HDN10255.

Four new tetrahydroanthracene derivatives (, -) and a known antibiotic, A-39183A (), were discovered from the marine-sponge-derived actinomycete HDN10255. Their structures including absolute configurations were elucidated based upon MS and NMR spectroscopic data, ECD calculations, and biogenetic considerations. Compounds and showed considerable cytotoxicity with the best IC value of 1.

Penispirozines A-H, Three Classes of Dioxopiperazine Alkaloids with Spirocyclic Skeletons Isolated from the Mangrove-Derived .

Eight new dioxopiperazine alkaloids, penispirozines A-H (-), were discovered from the mangrove-derived fungus HDN13-309. Their structures were elucidated by spectroscopic analysis, TDDFT-ECD calculations, and X-ray diffraction. Compound had an unusual pyrazino[1,2]oxazadecaline coupled with a thiophane ring system, and compound possessed a 6/5/6/5/6 pentacyclic ring system with two rare spirocyclic centers.

Correction: Undecylprodigiosin Induced Apoptosis in P388 Cancer Cells Is Associated with Its Binding to Ribosome.

[This corrects the article DOI: 10.1371/journal.pone.

Irregularly Bridged Epipolythiodioxopiperazines and Related Analogues: Sources, Structures, and Biological Activities.

Epipolythiodioxopiperazines (ETPs) are a class of biologically active fungal secondary metabolites characterized by a bridged polysulfide piperazine ring. Regularly, the sulfide functionality is attached in the α-positions of the dioxopiperazine scaffold. However, ETPs possessing irregular sulfur bridges have rarely been explored.

Chemoreactive-Inspired Discovery of Influenza A Virus Dual Inhibitor to Block Hemagglutinin-Mediated Adsorption and Membrane Fusion.

Owing to the emergence of drug resistance and high morbidity and mortality, the need for novel anti-influenza A virus (IAV) drugs with divergent targets is highly sought after. Herein, we reveal the discovery of an anti-IAV agent as a dual inhibitor to block hemagglutinin-mediated adsorption and membrane fusion using a chemoreactive -quinone methide (-QM) equivalent. Based on the -QM equivalent nonenzymatically multipotent behavior, we created a series of clavatol-derived pseudo-natural products and found that penindolone (PND), a new diclavatol indole adduct, exhibited potent and broad-spectrum anti-IAV activities with low risk of inducing drug resistance.

Identification of Gliotoxin isolated from marine fungus as a new pyruvate kinase M2 inhibitor.

Pyruvate kinase M2 (PKM2) functions as an important rate-limiting enzyme of aerobic glycolysis that is involved in tumor initiation and progression. However, there are few studies on effective PKM2 inhibitors. Gliotoxin is a marine-derived fungal secondary metabolite with multiple biological activities, including immunosuppression, cytotoxicity, and et al.

Trichothecin Inhibits Cancer-Related Features in Colorectal Cancer Development by Targeting STAT3.

Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that contributes to cancer progression through multiple processes of cancer development, which makes it an attractive target for cancer therapy. The IL-6/STAT3 pathway is associated with an advanced stage in colorectal cancer patients. In this study, we identified trichothecin (TCN) as a novel STAT3 inhibitor.

Antibacterial Polyketides from Antarctica Sponge-Derived Fungus sp. HDN151272.

Three new polyketides, ketidocillinones A-C (-), were discovered from the extract of an Antarctica sponge-derived fungus sp. HDN151272. All the structures were deduced by spectroscopic data, including NMR and HRESIMS.

Amphiepicoccins A-J: Epipolythiodioxopiperazines from the Fish-Gill-Derived Fungus HDN17-88.

Ten new epipolythiodioxopiperazines (ETPs), namely, amphiepicoccins A-J (-), were isolated from the fish-gill-derived fungus HDN17-88. Their structures were deduced from extensive spectroscopic data and electronic circular dichroism (ECD) calculations. Amphiepicoccin A () which contains an aromatic indole motif is unprecedented among the epicoccin type of ETPs.

Prenylated -Terphenyls from a Mangrove Endophytic Fungus, LDJ-5.

Nine previously undescribed prenylated -terphenyls, prenylterphenyllins F-J (, , -) and prenylcandidusins D-G (, -), were isolated from an endophytic fungus, LDJ-5. Their structures were determined from NMR and MS data. Differing from previously reported -terphenyls, compound represents a rare 6,5,6,6-fused ring system.

New metabolites from a Mariana Trench-derived actinomycete sp. HDN 17-237.

One new ,-butenoate derivative phenylbutenote (), and one new -pyrone nocapyrone T () were isolated from the deep-sea derived actinomycete sp. HDN 17-237. Their structures were elucidated by extensive HRMS, IR and NMR analyses.

Discovery of Two New Sorbicillinoids by Overexpression of the Global Regulator LaeA in a Marine-Derived Fungus YJ-11.

Overexpression of the global regulator LaeA in a marine-derived fungal strain of YJ-11 induced obvious morphological changes and metabolic variations. Further chemical investigation of the mutant strain afforded a series of sorbicillinoids including two new ones named 10,11-dihydrobislongiquinolide () and 10,11,16,17-tetrahydrobislongiquinolide (), as well as four known analogues, bislongiquinolide (), 16,17-dihydrobislongiquinolide (), sohirnone A (), and 2',3'-dihydrosorbicillin (). The results support that the global regulator LaeA is a useful tool in activating silent gene clusters in strains to obtain previously undiscovered compounds.

Secondary Metabolites Produced by Combined Culture of and a sp.

Four new alkyl aromatics, penixylarins A-D (-), along with the known biogenetically related 1,3-dihydroxy-5-(12-hydroxyheptadecyl)benzene () and 1,3-dihydroxy-5-(12-sulfoxyheptadecyl)benzene (), were isolated from a mixed culture of the Antarctic deep-sea-derived fungus PRB-2 and the mangrove-derived fungus sp. HDN13-249. UPLC-MS data and an analysis of structural features showed that compounds and were produced by collaboration of the two fungi, while compounds - could be produced by sp.

Secondary Metabolites from Deep-Sea Derived Microorganisms.

Microorganisms obtained from the deep sea are a rich source of marine natural products with distinctive chemical structures and bioactivities. In this review, we will provide a retrospective of outstanding research within the scope of deep-sea (≥1000 m) microbial natural products, which has produced up to 442 compounds by the end of 2017. Approximetely, 60% of these structures have demonstrated various biological activities with more than 30% showing cytotoxic function.

Anthraquinone Derivatives from a Marine-Derived Fungus HDN16-802.

Five new anthraquinone derivatives, auxarthrols D-H (-), along with two known analogues (-), were obtained from the culture of the marine-derived fungus . Their structures, including absolute configurations, were established on the basis of NMR, HRESIMS, and circular dichroism (CD) spectroscopic techniques. Among them, compound represents the second isolated anthraquinone derivative with a chlorine atom, which, with compound , are the first reported anthraquinone derivatives with anticoagulant activity.

New Glutamine-Containing Azaphilone Alkaloids from Deep-Sea-Derived Fungus HDN151398.

Three new azaphilone alkaloids containing glutamine residues, namely -glutarylchaetoviridins A-C (-), together with two related compounds ( and ) were isolated from the extract of HDN151398, a fungus isolated from a deep-sea sediment sample collected in South China Sea. Their structures were elucidated on the basis of extensive 1D and 2D NMR as well as HRESIMS spectroscopic data and chemical analysis. -glutarylchaetoviridins A-C (-) represent the first class of chaetoviridins characterized by embedded glutamate residues.

Aspergiolides A and B: Core Structural Establishment and Synthesis of Structural Analogues.

The core structure of marine natural products aspergiolides A (1a) and B (1b) was achieved via a concise, two-step procedure with satisfactory yield. Based on this protocol, a natural products mimic library containing 25 structural simplified analogues of 1a was then constructed. Several prepared analogues showed potential cytotoxic activity against five different tumor cell lines, and compound 7bb, in particular, exhibited cytotoxicity comparable to that of 1a.