Screening, Discovery, and Optimization of the Natural Antitubercular Chlorflavonin from a Marine-Derived Fungal Library.

Tuberculosis (TB), caused by the bacterium (), is still a leading cause of mortality worldwide. Fifty-fungi from a marine-derived fungal library were screened for anti- activity, and an strain with strong anti- activity was found. Three known flavones, chlorflavonin (), dechlorflavonin (), and bromoflavone (), were isolated from this fungus.

Identification and Experimental Validation of Prognostic miRNA Signature and Ferroptosis-Related Key Genes in Cervical Squamous Cell Carcinoma.

Objectives: This study aimed to investigate the prognostic value of miRNAs and ferroptosis-related genes in cervical squamous cell carcinoma.

Methods: We mined data from public databases for differentially expressed miRNAs, ferroptosis-related genes, and clinical parameters and constructed a prognostic risk model. The predictive performance of the model was evaluated using survival and receiver operating characteristic curve analyses.

Semisynthesis, Structure Elucidation and Anti- Activity of a Series of Marine-Derived 14-Membered Resorcylic Acid Lactones with Interesting Ketal Groups.

The incidence of infection is on the rise; however, the existing drug treatment cycle is lengthy and often requires multi-drug combination. Therefore, there is a need to develop new and effective anti- drugs. Cochliomycin A, a 14-membered resorcylic acid lactone with an acetonide group at C-5' and C-6', exhibits a wide range of antimicrobial, antimalarial, and antifouling activities.

A Terphenyllin Derivative CHNQD-00824 from the Marine Compound Library Induced DNA Damage as a Potential Anticancer Agent.

With the emergence of drug resistance and the consequential high morbidity and mortality rates, there is an urgent need to screen and identify new agents for the effective treatment of cancer. Terphenyls-a group of aromatic hydrocarbons consisting of a linear 1,4-diaryl-substituted benzene core-has exhibited a wide range of biological activities. In this study, we discovered a terphenyllin derivative-CHNQD-00824-derived from the marine compound library as a potential anticancer agent.

Malignant rhabdoid tumor of the omentum in an adult male: a case report and literature review.

Malignant rhabdoid tumors (MRTs) are rare tumors with high mortality rates and poor prognoses. MRTs occur mainly in the central nervous system, kidneys, and soft tissues, but rarely in the omentum. MRTs occur more commonly in infants and children and less frequently in adults.

Discovery of a natural small-molecule AMP-activated kinase activator that alleviates nonalcoholic steatohepatitis.

Unlabelled: Non-alcoholic steatohepatitis (NASH) is a primary cause of cirrhosis and hepatocellular carcinoma. Unfortunately, there is no approved drug treatment for NASH. AMP-activated kinase (AMPK) is an important metabolic sensor and whole-body regulator.

Analogues of natural products yaequinolones as potential inflammatory inhibitors: Design, synthesis and biological evaluation.

Inflammation is connected with a variety of diseases and there is still a need to develop more effective and safer anti-inflammatory drugs. Herein, we synthesized, resolved, and characterized eight enantiopure isomers of yaequinolone J1 (1), yaequinolone J2 (2), 4'-desmethoxyyaequinolone J1 (3), and 4'-desmethoxyyaequinolone J2 (4). The key synthetic steps were extended and 34 racemic analogues modified at the 4-aryl, the N-position, and the pyran ring were designed and synthesized.

Targeted isolation of antitubercular cycloheptapeptides and an unusual pyrroloindoline-containing new analog, asperpyrroindotide A, using LC-MS/MS-based molecular networking.

Unlabelled: Further insights on the secondary metabolites of a soft coral-derived fungus under the guidance of MS/MS-based molecular networking led to the isolation of seven known cycloheptapeptides, namely, asperversiamides A-C (-) and asperheptatides A-D (-) and an unusual pyrroloindoline-containing new cycloheptapeptide, asperpyrroindotide A (). The structure of was elucidated by comprehensive spectroscopic data analysis, and its absolute configuration was determined by advanced Marfey's method. The semisynthetic transformation of into was successfully achieved and the reaction conditions were optimized.

Scalable total synthesis of (+)-aniduquinolone A and its acid-catalyzed rearrangement to aflaquinolones.

The strong antibacterial, antiviral and anticancer activities demonstrated by quinolones make them promising lead structures and important synthetic targets for drug discovery. Here, we report, to the best of our knowledge, the first scalable total synthesis of antiviral (+)-aniduquinolone A, possessing a 3,4-dioxygenated 5-hydroxy-4-aryl-quinolin-2(1H)-one skeleton. This synthetic strategy explores E-stereoselective Horner-Wadsworth-Emmons (HWE) olefination as the key step to assemble isopropenyl substituted tetrahydrofuran onto the 3,4-dioxygenated 5-hydroxy-4-aryl-quinolin-2(1H)-one core, which is built by highly diastereoselective intramolecular aldol reaction.

Discovery, total syntheses and potent anti-inflammatory activity of pyrrolinone-fused benzoazepine alkaloids Asperazepanones A and B from Aspergillus candidus.

Natural products are well established as an important resource and play an important role in drug discovery. Here, two pyrrolinone-fused benzoazepine alkaloids, (+)-asperazepanones A (1) and B (2) with a 6/7/5 ring system, together with the artifact (-)-asperazepanone A (1), were isolated from the coral-derived Aspergillus candidus fungus. Their structures including absolute configurations were elucidated by extensive spectroscopic methods, single crystal X-ray diffraction, and ECD calculations.

Design and Characterization of a Natural Arf-GEFs Inhibitor Prodrug with Potent Anti-Hepatocellular Carcinoma Efficacy .

Brefeldin A (BFA), a well-known natural Arf-GEFs inhibitor, is effective against hepatocellular carcinoma (HCC), while the poor solubility, serious toxicity, and short half-life limit its potential. Herein, distinct corresponding prodrugs of BFA, including esters -, carbonates - and -, and carbamates -, were synthesized and evaluated. () with improved aqueous solubility (15-20 mg/mL) demonstrated favorable pharmacokinetic profiles.

Integrating Activity-Guided Strategy and Fingerprint Analysis to Target Potent Cytotoxic Brefeldin A from a Fungal Library of the Medicinal Mangrove .

Mangrove-associated fungi are rich sources of novel and bioactive compounds. A total of 102 fungal strains were isolated from the medicinal mangrove collected from the South China Sea. Eighty-four independent culturable isolates were identified using a combination of morphological characteristics and internal transcribed spacer (ITS) sequence analyses, of which thirty-seven strains were selected for phylogenetic analysis.

New brefeldin A-cinnamic acid ester derivatives as potential antitumor agents: Design, synthesis and biological evaluation.

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and ranks third in mortality rate worldwide. Brefeldin A (BFA, 1), a natural Arf1 inhibitor, qualifies extremely superior antitumor activity against HCC while its low aqueous solubility, poor bioavailability, and high toxicity have greatly hindered its translation to the clinic. Herein, a series of BFA-cinnamic acid ester derivatives was rationally designed and synthesized via introducing active cinnamic acid and its analogues into the structure of 1.

Design, Semisynthesis, Insecticidal and Antibacterial Activities of a Series of Marine-Derived Geodin Derivatives and Their Preliminary Structure-Activity Relationships.

To enhance the biological activity of the natural product geodin (), isolated from the marine-derived fungus sp., a series of new ether derivatives (-) was designed and semisynthesized using a high-yielding one-step reaction. In addition, the insecticidal and antibacterial activities of all geodin congeners were evaluated systematically.

Trends of antimalarial marine natural products: progresses, challenges and opportunities.

Covering 1972 to 2021Malaria remains a significant public health problem in some regions of the world. The great efforts to control malaria have been severely compromised due to the widespread resistance of to nearly all frontline drugs. Pursuit of novel molecules from the sea will potentially result in new interventions against malaria, which are urgently needed to combat the increase of resistance.

Semisynthesis and biological evaluation of (+)-sclerotiorin derivatives as antitumor agents for the treatment of hepatocellular carcinoma.

Hepatocellular carcinoma is one of the most common primary hepatic malignancy. Herein, a series of semisynthesized derivatives (2-30) of the natural product (+)-sclerotiorin (1) was prepared and evaluated the cytotoxic activities against six cancer cell lines. Among them, 3 and 5 were the most effective compounds against human hepatocellular carcinoma Bel-7402 cell line with IC values of 1.

Semi-Synthesis, Cytotoxic Evaluation, and Structure-Activity Relationships of Brefeldin A Derivatives with Antileukemia Activity.

Brefeldin A (), a potent cytotoxic natural macrolactone, was produced by the marine fungus sp. (HS-N-29) from the medicinal mangrove . Series of its ester derivatives - were designed and semi-synthesized, and their structures were characterized by spectroscopic methods.

Discovery of penipanoid C-inspired 2-(3,4,5-trimethoxybenzoyl)quinazolin-4(3H)-one derivatives as potential anticancer agents by inhibiting cell proliferation and inducing apoptosis in hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is the most common form of liver cancer and the fourth leading cause of cancer-related death worldwide. First-line drugs such as sorafenib provide only a modest benefit to HCC patients. In this study, the gram-scale synthesis of 2-benzoylquinazolin-4(3H)-one skeleton was achieved successfully via the I/DMSO catalytic system.

Structure modification, antialgal, antiplasmodial, and toxic evaluations of a series of new marine-derived 14-membered resorcylic acid lactone derivatives.

Unlabelled: Marine natural products play critical roles in the chemical defense of many marine organisms and are essential, reputable sources of successful drug leads. Sixty-seven 14-membered resorcylic acid lactone derivatives - and - of the natural product zeaenol () isolated from the marine-derived fungus were semisynthesized by chlorination, acylation, esterification, and acetalization in one to three steps. The structures of these new derivatives were established by HRESIMS and NMR techniques.

Brefeldin A Induces Apoptosis, Inhibits BCR-ABL Activation, and Triggers BCRABL Degradation in Chronic Myeloid Leukemia K562 Cells.

Background: Chronic Myeloid Leukemia (CML) is a myeloproliferative disease caused by BCR-ABL oncoprotein. Tyrosine kinase inhibitors have been developed to inhibit the activity of BCR-ABL; however, drug resistance and side effect occur in clinic application. Therefore, it is urgent to find novel drugs for CML treatment.

The intriguing chemistry and biology of sulfur-containing natural products from marine microorganisms (1987-2020).

Unlabelled: Natural products derived from marine microorganisms have received great attention as a potential resource of new compound entities for drug discovery. The unique marine environment brings us a large group of sulfur-containing natural products with abundant biological functionality including antitumor, antibiotic, anti-inflammatory and antiviral activities. We reviewed all the 484 sulfur-containing natural products (non-sulfated) isolated from marine microorganisms, of which 59.

17-Hydroxybrevianamide N and Its N1-Methyl Derivative, Quinazolinones from a Soft-Coral-Derived sp. Fungus: 13 Enantiomers as the True Natural Products.

Under the guidance of MS/MS-based molecular networking and HPLC-UV, two new alkaloid racemates, (±)-17-hydroxybrevianamide N () and (±)-N1-methyl-17-hydroxybrevianamide N (), featuring a rare -hydroxyphenylalanine residue and an imide subunit, were isolated from a soft-coral-derived sp. fungus. The true natural products (+)- and (+)- were further monitored and obtained from the freshly prepared EtOAc extracts, while (-)- and (-)- are artifacts generated during extraction and purification processes.

Targeted Isolation of Asperheptatides from a Coral-Derived Fungus Using LC-MS/MS-Based Molecular Networking and Antitubercular Activities of Modified Cinnamate Derivatives.

Under the guidance of MS/MS-based molecular networking, four new cycloheptapeptides, namely, asperheptatides A-D (-), were isolated together with three known analogues, asperversiamide A-C (-), from the coral-derived fungus . The planar structures of the two major compounds, asperheptatides A and B ( and ), were determined by comprehensive spectroscopic data analysis. The absolute configurations of the amino acid residues were determined by advanced Marfey's method.

Circadian Clock Protein PERIOD2 Suppresses the PI3K/Akt Pathway and Promotes Cisplatin Sensitivity in Ovarian Cancer.

Background: The mortality rate of ovarian cancer is the highest among gynecological tumors. The two factors leading to high mortality of ovarian cancer are late clinical stage and chemotherapy resistance. It is very important to reverse or intervene chemotherapy resistance.