Malyngamide X: The First (7R)‐Lyngbic Acid that Connects to a New Tripeptide Backbone from the Thai Sea Hare Bursatella leachii

Malyngamide X ( 1 ), the first (7R)‐lyngbic acid connected to a new tripeptide backbone, was isolated from the Thai sea hare Bursatella leachii. The gross structure of 1 was established on the basis of 1D and 2D NMR and mass spectroscopic data. Combination of the NMR spectroscopic experiments with α‐methoxy‐α‐(trifluoromethyl)phenylacetic acid esters, 2,2,2‐trifluoro‐1‐(9‐anthryl)ethanol chiral solvating agent, and molecular mechanics of 1 and the synthetic molecular fragments allowed us to determine the absolute stereochemistry of all six stereogenic centers without hydrolytic degradation of the compound. Compound 1 displayed moderate cytotoxic, antitubercular, and antimalarial properties.     

Analysis of tetracycline antibiotics using HPLC with pulsed amperometric detection.

The analysis of tetracycline, oxytetracyline, chlortetracycline and doxycycline by high-performance liquid chromatography with pulsed amperometric detection using an anodized boron-doped diamond thin film (BDD) electrode is originally reported. The analyses were carried out using the mobile phase, phosphate buffer (0.01 M, pH 2.5)-acetonitrile (80:20; v/v), on a C18 column (250 x 4.6 mm i.d., 5 microm) at a flow rate of 1.0 mL/min. The optimal PAD waveform parameters at the anodized BDD were 1.5 V (versus Ag/AgCl) detection potential (E(det)) for 290 ms (200 ms delay time and 90 ms integration time), 2.0 V (versus Ag/AgCl) oxidation potential (E(oxd)) for 200 ms oxidation time (t(oxd)) and 0.4 V (versus Ag/AgCI) reduction potential (E(red)) for 200 ms reduction time (t(red)). The proposed method showed the simultaneous determination of tetracycline, oxytetracyline, chlortetracycline and doxycycline with a linear range of 0.1 - 100 microg/mL, detection limits of 0.05 - 0.1 microg/mL and recoveries of 70.8 - 96.0%. The application of this method to real samples was demonstrated and validated using a shrimp sample.     

Barium(II)–2,4‐dinitrophenolate–18‐crown‐6 at 183 K

The title compound, bis(2,4‐dinitrophenolato‐κ²O,O′)(1,4,7,10,13,16‐hexaoxadecane‐κ⁶O)barium(II), [Ba(C₆H₃N₂O₅)₂(C₁₂H₂₄O₆)], is a 1:1 complex of barium(II)–2,4‐di­nitro­phenolate and 1,4,7,10,13,16‐hexaoxa­cyclo­octa­decane (18‐crown‐6). Its structure is located on a crystallographic inversion centre. The temperature dependence of the crystal structure has been studied. The monoclinic β angle of the P2₁/­n space group increases with increasing temperature. The packing structure of the complex is stabilized by intermolecular C—H?O interactions.     

1‐Acetyl‐3′‐(4‐bromophenyl)‐3′‐chlorospiro[3H‐indole‐3,2′‐oxetan]‐2(1H)‐one

In the title compound, C₁₈H₁₃BrClNO₃, the heterocyclic ring of the indole is distorted from planarity towards an envelope conformation. The orientations of the indole, oxetane, chloro and bromo­phenyl substituents are conditioned by the sp³ states of the spiro‐junction and the Cl‐attached C atoms.     

Di‐2‐pyridyl ketone N4,N4‐(butane‐1,4‐diyl)thiosemicarbazone

The title compound, C₁₆H₁₇N₅S, is in the thione form and crystallizes with two independent mol­ecules in the asymmetric unit. In both mol­ecules, the penta­methyl­ene­imine five‐membered ring adopts an envelope conformation, and in one of the molecules this ring shows positional disorder. The thione S and hydrazine N atoms are in the Z configuration with respect to the C—N bond.     

Structural Basis of 2-Phenylamino-4-phenoxyquinoline Derivatives as Potent HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors

New target molecules, namely, 2-phenylamino-4-phenoxyquinoline derivatives, were designed using a molecular hybridization approach, which was accomplished by fusing the pharmacophore structures of three currently available drugs: nevirapine, efavirenz, and rilpivirine. The discovery of disubstituted quinoline indicated that the pyridinylamino substituent at the 2-position of quinoline plays an important role in its inhibitory activity against HIV-1 RT. The highly potent HIV-1 RT inhibitors, namely, 4-(2′,6′-dimethyl-4′-formylphenoxy)-2-(5″-cyanopyridin-2″ylamino)quinoline (6b) and 4-(2′,6′-dimethyl-4′-cyanophenoxy)-2-(5″-cyanopyridin-2″ylamino)quinoline (6d) exhibited half-maximal inhibitory concentrations (IC50) of 1.93 and 1.22 µM, respectively, which are similar to that of nevirapine (IC50 = 1.05 µM). The molecular docking results for these two compounds showed that both compounds interacted with Lys101, His235, and Pro236 residues through hydrogen bonding and interacted with Tyr188, Trp229, and Tyr318 residues through π–π stacking in HIV-1 RT. Interestingly, 6b was highly cytotoxic against MOLT-3 (acute lymphoblastic leukemia), HeLA (cervical carcinoma), and HL-60 (promyeloblast) cells with IC50 values of 12.7 ± 1.1, 25.7 ± 0.8, and 20.5 ± 2.1 µM, respectively. However, 6b and 6d had very low and no cytotoxicity, respectively, to-ward normal embryonic lung (MRC-5) cells. Therefore, the synthesis and biological evaluation of 2-phenylamino-4-phenoxyquinoline derivatives can serve as an excellent basis for the development of highly effective anti-HIV-1 and anticancer agents in the near future.     

Anticancer Effects and Molecular Action of 7-α-Hydroxyfrullanolide in G2/M-Phase Arrest and Apoptosis in Triple Negative Breast Cancer Cells

Triple negative breast cancer (TNBC) is a breast cancer subtype characterized by the absence of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 expression. TNBC cells respond poorly to targeted chemotherapies currently in use and the mortality rate of TNBC remains high. Therefore, it is necessary to identify new chemotherapeutic agents for TNBC. In this study, the anti-cancer effects of 7-α-hydroxyfrullanolide (7HF), derived from Grangea maderaspatana, on MCF-7, MDA-MB-231 and MDA-MB-468 breast cancer cells were assessed using MTT assay. The mode of action of 7HF in TNBC cells treated with 6, 12 and 24 µM of 7HF was determined by flow cytometry and propidium iodide (PI) staining for cell cycle analysis and annexin V/fluorescein isothiocyanate + PI staining for detecting apoptosis. The molecular mechanism of action of 7HF in TNBC cells was investigated by evaluating protein expression using proteomic techniques and western blotting. Subsequently, 7HF exhibited the strongest anti-TNBC activity toward MDA-MB-468 cells and a concomitantly weak toxicity toward normal breast cells. The molecular mechanism of action of low-dose 7HF in TNBC cells primarily involved G2/M-phase arrest through upregulation of the expression of Bub3, cyclin B1, phosphorylated Cdk1 (Tyr 15) and p53-independent p21. Contrastingly, the upregulation of PP2A-A subunit expression may have modulated the suppression of various cell survival proteins such as p-Akt (Ser 473), FoxO3a and β-catenin. The concurrent apoptotic effect of 7HF on the treated cells was mediated via both intrinsic and extrinsic modes through the upregulation of Bax and active cleaved caspase-7–9 expression and downregulation of Bcl-2 and full-length caspase-7–9 expression. Notably, the proteomic approach revealed the upregulation of the expression of pivotal protein clusters associated with G1/S-phase arrest, G2/M-phase transition and apoptosis. Thus, 7HF exhibits promising anti-TNBC activity and at a low dose, it modulates signal transduction associated with G2/M-phase arrest and apoptosis.     

Fungus-Derived 3-Hydroxyterphenyllin and Candidusin A Ameliorate Palmitic Acid-Induced Human Podocyte Injury via Anti-Oxidative and Anti-Apoptotic Mechanisms

Diabetic nephropathy (DN) is a leading cause of end-stage renal disease. An elevated fatty acid plasma concentration leads to podocyte injury and DN progression. This study aimed to identify and characterize cellular mechanisms of natural compounds that inhibit palmitic acid (PA)–induced human podocyte injury. By screening 355 natural compounds using a cell viability assay, 3-hydroxyterphenyllin (3-HT) and candidusin A (CDA), isolated from the marine-derived fungus Aspergillus candidus PSU-AMF169, were found to protect against PA-induced podocyte injury, with half-maximal inhibitory concentrations (IC₅₀) of ~16 and ~18 µM, respectively. Flow cytometry revealed that 3-HT and CDA suppressed PA-induced podocyte apoptosis. Importantly, CDA significantly prevented PA-induced podocyte barrier impairment as determined by 70 kDa dextran flux. Reactive oxygen species (ROS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) direct scavenging assays indicated that both compounds exerted an anti-oxidative effect via direct free radical–scavenging activity. Moreover, 3-HT and CDA upregulated the anti-apoptotic Bcl2 protein. In conclusion, 3-HT and CDA represent fungus-derived bioactive compounds that have a novel protective effect on PA-induced human podocyte apoptosis via mechanisms involving free radical scavenging and Bcl2 upregulation.     

Conoideoxime A,antibacterial bis-oxime prenyl-tryptophan dimer from the whitefly pathogenic fungus Conoideocrella luteorostrata BCC 76664

Conoideoxime A (1), a prenyl-tryptophan dimer possessing bis-oxime functionality, was isolated from cultures of the whitefly pathogenic fungus Conoideocrella luteorostrata BCC 76664. The structure was elucidated by spectroscopic analyses. It displayed antibacterial activity against Gram-positive bacteria, Bacillus cereus, Enterococcus faecium, and Staphylococcus aureus, with MIC values of 3.13, 6.25, and 6.25?μg/mL, respectively.