Multifunctional Protein Hybrid Nanoplatform for Synergetic Photodynamic-Chemotherapy of Malignant Carcinoma by Homologous Targeting Combined with Oxygen Transport.

Photodynamic therapy (PDT) under hypoxic conditions and drug resistance in chemotherapy are perplexing problems in anti-tumor treatment. In addition, central nervous system neoplasm-targeted nanoplatforms are urgently required. To address these issues, a new multi-functional protein hybrid nanoplatform is designed, consisting of transferrin (TFR) as the multicategory solid tumor recognizer and hemoglobin for oxygen supply (ODP-TH). This protein hybrid framework encapsulates the photosensitizer protoporphyrin IX (PpIX) and chemotherapeutic agent doxorubicin (Dox), which are attached by a glutathione-responsive disulfide bond. Mechanistically, ODP-TH crosses the blood-brain barrier (BBB) and specifically aggregated in hypoxic tumors via protein homology recognition. Oxygen and encapsulated drugs ultimately promote a therapeutic effect by down-regulating the abundance of multidrug resistance gene 1 (MDR1) and hypoxia-inducible factor-1-α (HIF-1α). The results reveal that ODP-TH achieves oxygen transport and protein homology recognition in the hypoxic tumor occupation. Indeed, compared with traditional photodynamic chemotherapy, ODP-TH achieves a more efficient tumor-inhibiting effect. This study not only overcomes the hypoxia-related inhibition in combination therapy by targeted oxygen transport but also achieves an effective treatment of multiple tumors, such as breast cancer and glioma, providing a new concept for the construction of a promising multi-functional targeted and intensive anti-tumor nanoplatform.

Antibacterial Prenylated p-Hydroxybenzoic Acid Derivatives from Oberonia myosurus and Identification of Putative Prenyltransferases.

Twelve hitherto unknown tandem prenylated p-hydroxybenzoic acid derivatives, namely, oberoniamyosurusins A-L, together with five known derivatives, were isolated from an EtOH extract of the whole parts of the plant Oberonia myosurus. Compounds 10, 13, and 17 exhibited moderate inhibitory activity against Staphylococcus aureus subsp. aureus ATCC29213 with MIC50 values ranging from 7.6 to 23 µg/mL. To determine the biosynthetic pathway of this class of tandem prenyl-substituted compounds, the full-length transcriptome of O. myosurus was sequenced, yielding 19.09 Gb of clean data and 10 949 nonredundant sequences. Two isoforms of p-hydroxybenzoic acid prenyltransferases were annotated and functionally characterized as the enzymes that might be involved in the biosynthesis of nervogenic acid (13) in Pichia pastoris.

Three new 2,5-diketopiperazines from the fish intestinal Streptomyces sp. MNU FJ-36.

The gut actinobacteria of marine-inhabited fish is one of the most important reservoirs of novel natural products. Currently, the Streptomyces sp. MNU FJ-36 was isolated from the intestinal fabric of Katsuwonus sp. and determined by 16S rRNA analysis. From the cultures of the S. sp. MNU FJ-36, three new 2,5-diketopiperazines (2,5-DKPs) were discovered and identified as 3-(3-hydroxy-4-methoxybenzyl)-6-isobutyl-2,5-diketopiperazine (1), 3-(1,3-benzodioxol-5-ylmethyl)-6-isobutyl-2,5-diketopiperazine (2) and 3-(1,3-benzodioxol-5-ylmethyl)-6-isopropyl-2,5-diketopiperazine (3). Their structures were elucidated on the basis of spectroscopic data analysis. All the compounds were also evaluated for their inhibitory activity against P388, A-549 and HCT-116 cell lines with the MTT assay.

Chemical constituents from the stem bark of Trewia nudiflora L. and their antioxidant activities.

Three new compounds, namely, (+)-dihydrodehydrodiconiferyl alcohol 4- O- beta-(6''- O-galloyl)-glucopyranoside ( 1), 4,4'- O-dimethylellagic acid 3-(2''- O-acetyl)- alpha-rhamnopyranoside ( 2), and ethyl O- beta-(6'-galloyl)-glucopyranoside ( 3), together with eleven known ones, were isolated from the stem bark of Trewia nudiflora. Their structures were elucidated by means of 1D, 2 D NMR and HR-MS analyses. The antioxidant activities of these compounds were evaluated with the DPPH radical-scavenging assay. Compound 1 showed significant antioxidant activity. In addition, compounds 1, 2 and 3 rescued the H (2)O (2)-induced PC12 cell death at 0.4 microM in the MTT assay.

Tricycloalternarene derivatives produced by an endophyte alternaria alternata isolated from Maytenus hookeri.

A new tricycloalternarene derivative, named tricycloalternarenal (1), together with three known compounds was isolated from the cultures of Alternaria alternata, an endophytic fungus in the leaves of the plant Maytenus hooker! (Celastraceae). Structure of 1 was established as (2E)-6-(3, 3a, 5, 6, 7, 8, 9, 9a-octahydro-5-hydroxy-3a-methyl-8-oxo-cyclo-penta[b]chromen-1-yl)-2-methylhept-2-enal by spectroscopic methods, including 2D-NMR experiments. The remaining compounds were determined as tricycloalternarene-3b (2), alterperylenol (3), and dihydroalterperylenol (4).