Taxifolin stability: In silico prediction and in vitro degradation with HPLC-UV/UPLC–ESI-MS monitoring

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Characterization of Planktochlorella nurekis Extracts and Virucidal Activity against a Coronavirus Model, the Murine Coronavirus 3

Certain members of the Coronaviridae family have emerged as zoonotic agents and have recently caused severe respiratory diseases in humans and animals, such as SARS, MERS, and, more recently, COVID-19. Antivirals (drugs and antiseptics) capable of controlling viruses at the site of infection are scarce. Microalgae from the Chlorellaceae family are sources of bioactive compounds with antioxidant, antiviral, and antitumor activity. In the present study, we aimed to evaluate various extracts from Planktochlorella nurekis in vitro against murine coronavirus-3 (MHV-3), which is an essential human coronavirus surrogate for laboratory assays. Methanol, hexane, and dichloromethane extracts of P. nurekis were tested in cells infected with MHV-3, and characterized by UV-vis spectrophotometry, nuclear magnetic resonance (NMR) spectroscopy, ultraperformance liquid chromatography-mass spectrometry (UPLC-MS), and the application of chemometrics through principal component analysis (PCA). All the extracts were highly efficient against MHV-3 (more than a 6 Log unit reduction), regardless of the solvent used or the concentration of the extract, but the dichloromethane extract was the most effective. Chemical characterization by spectrophotometry and NMR, with the aid of statistical analysis, showed that polyphenols, carbohydrates, and isoprene derivatives, such as terpenes and carotenoids have a more significant impact on the virucidal potential. Compounds identified by UPLC-MS were mainly lipids and only found in the dichloromethane extract. These results open new biotechnological possibilities to explore the biomass of P. nurekis; it is a natural extract and shows low cytotoxicity and an excellent antiviral effect, with low production costs, highlighting a promising potential for development and implementation of therapies against coronaviruses, such as SARS-CoV-2.This research was funded LVA-MIP-CCB-UFSC/Sigpex: 201917940, and CNPq, CAPES-DS

Search for antimicrobial activity among fifty-two natural and synthetic compounds identifies anthraquinone and polyacetylene classes that inhibit Mycobacterium tuberculosis

Drug-resistant tuberculosis threatens to undermine global control programs by limiting treatment options. New antimicrobial drugs are required, derived from new chemical classes. Natural products offer extensive chemical diversity and inspiration for synthetic chemistry. Here, we isolate, synthesize and test a library of 52 natural and synthetic compounds for activity against Mycobacterium tuberculosis. We identify seven compounds as antimycobacterial, including the natural products isobavachalcone and isoneorautenol, and a synthetic chromene. The plant-derived secondary metabolite damnacanthal was the most active compound with the lowest minimum inhibitory concentration of 13.07 μg/mL and a favorable selectivity index value. Three synthetic polyacetylene compounds demonstrated antimycobacterial activity, with the lowest MIC of 17.88 μg/mL. These results suggest new avenues for drug discovery, expanding antimicrobial compound chemistries to novel anthraquinone and polyacetylene scaffolds in the search for new drugs to treat drug-resistant bacterial diseases

Pyridinoacridine alkaloids of marine origin: NMR and MS spectral data, synthesis, biosynthesis and biological activity

This review focuses on pyridoacridine-related metabolites as one biologically interesting group of alkaloids identified from marine sources. They are produced by marine sponges, ascidians and tunicates, and they are structurally comprised of four to eight fused rings including heterocycles. Acridine, acridone, dihydroacridine, and quinolone cores are features regularly found in these alkaloid skeletons. The lack of hydrogen atoms next to quaternary carbon atoms for two or three rings makes the chemical shift assignment a difficult task. In this regard, one of the aims of this review is the compilation of previously reported, pyridoacridine 13C NMR data. Observations have been made on the delocalization of electrons and the presence of some functional groups that lead to changes in the chemical shift of some carbon resonances. The lack of mass spectra information for these alkaloids due to the compactness of their structures is further discussed. Moreover, the biosynthetic pathways of some of these metabolites have been shown since they could inspire biomimetic synthesis. The synthesis routes used to prepare members of these marine alkaloids (as well as their analogues), which are synthesized for biological purposes are also discussed. Pyridoacridines were found to have a large spectrum of bioactivity and this review highlights and compares the pharmacophores that are responsible for the observed bioactivity

Quantitative Structure Inter-Activity Relationship (QSInAR). Cytotoxicity Study of Some Hemisynthetic and Isolated Natural Steroids and Precursors on Human Fibrosarcoma Cells HT1080

Combined experimental and quantitative structure inter-activity relationship (QSIAR) computation methods were advanced in order to establish the structural and mechanistic influences that steroids and triterpenes, either as newly synthesized or naturally isolated products, have on human HT1080 mammalian cancer cells. The main Hansch structural indicators such as hydrophobicity (LogP), polarizability (POL) and total energy (Etot) were considered and both the structure-projected as well as globally computed correlations were reported; while the inter-activity correlation of the global activity with those projected on structural information was revealed as equal to the direct structural-activity one for the trial sets of compounds, the prediction for the testing set of molecules reported even superior performances respecting those characteristic for the calibration set, validating therefore the present QSInAR models; accordingly, it follows that the LogP carries the most part of the cytotoxic signal, while POL has little influence on inhibiting tumor growth—A complementary behavior with their earlier known influence on genotoxic carcinogenesis. Regarding the newly hemisynthetic compounds it was found that stigmasta-4,22-dien-3-one is not adapted for cell membrane diffusion; it is recommended that aminocinnamyl chlorohydrate be further modified in order to acquire better steric influence, while aminocinnamyl-2,3,4,6-O-tétraacétyl-α-D-glucopyranoside was identified as being inhibited in the tumor cell by other molecular mechanisms–here not revealed–although it has a moderate-high anti-cancer structurally predicted activity

Tanzawaic acids I–L : four new polyketides from Penicillium sp. IBWF104-06

Four new polyketides have been identified in culture filtrates of the fungal strain Penicillium sp. IBWF104-06 isolated from a soil sample. They are structurally based on the same trans-decalinpentanoic acid skeleton as tanzawaic acids A–H. One of the new compounds was found to inhibit the conidial germination in the rice blast fungus Magnaporthe oryzae at concentrations of 25 μg/mL

SF002-96-1, a new drimane sesquiterpene lactone from an Aspergillus species, inhibits survivin expression

Survivin, a member of the IAP (inhibitor of apoptosis) gene family, is overexpressed in virtually all human cancers and is functionally involved in the inhibition of apoptosis, regulation of cell proliferation, metastasis and resistance to therapy. Because of its upregulation in malignancy, survivin has currently attracting considerable interest as a new target for anticancer therapy. In a screening of approximately 200 strains of imperfect fungi for the production of inhibitors of survivin promoter activity, a new drimane sesquiterpene lactone, SF002-96-1, was isolated from fermentations of an Aspergillus species. The compound inhibited survivin promoter activity in transiently transfected Colo 320 cells in a dose dependent manner with IC(50) values of 3.42 µM (1.3 µg/mL). Moreover, it also reduced mRNA levels and protein synthesis of survivin and triggered apoptosis