Synthesis and Bioactivity of Ancorinoside B, A Marine Diglycosyl Tetramic Acid

The sponge metabolite ancorinoside B was prepared for the first time in 16 steps and 4% yield. It features a β-d-galactopyranosyl-(1→4)-β-d-glucuronic acid tethered to a d-aspartic acid-derived tetramic acid. Key steps were the synthesis of a fully protected d-lactose derived thioglycoside, its attachment to a C20-aldehyde spacer, functionalization of the latter with a terminal N-(β-ketoacyl)-d-aspartate, and a basic Dieckmann cyclization to close the pyrrolidin-2,4-dione ring with concomitant global deprotection. Ancorinoside B exhibited multiple biological effects of medicinal interest. It inhibited the secretion of the cancer metastasis-relevant matrix metalloproteinases MMP-2 and MMP-9, and also the growth of Staphylococcus aureus biofilms by ca 87% when applied at concentrations as low as 0.5 µg/mL. This concentration is far below its MIC of ca 67 µg/mL and thus unlikely to induce bacterial resistance. It also led to a 67% dispersion of preformed S. aureus biofilms when applied at a concentration of ca 2 µg/mL. Ancorinoside B might thus be an interesting candidate for the control of the general hospital, catheter, or joint protheses infections.

Download Full-text

Biosynthetic strategies for tetramic acid formation

Natural Product Reports ◽

10.1039/d0np00099j ◽

2021 ◽

Author(s):

Xuhua Mo ◽

Tobias A. M. Gulder

Keyword(s):

Molecular Mechanism ◽

Gene Clusters ◽

Acid Formation ◽

Biosynthetic Gene ◽

Tetramic Acid ◽

Biosynthetic Gene Clusters ◽

The Individual ◽

First Time ◽

Acid Unit

Over 30 biosynthetic gene clusters for natural tetramate have been identified. This highlight reviews the biosynthetic strategies for formation of tetramic acid unit for the first time, discussing the individual molecular mechanism in detail.

Download Full-text

Characterization of R‐pyocin activity against Gram‐positive pathogens for the first time with special focus on Staphylococcus aureus

Journal of Applied Microbiology ◽

10.1111/jam.15134 ◽

2021 ◽

Author(s):

Alzhraa Ali Mohamed ◽

Ashraf M. Elshawadfy ◽

Gehan Amin ◽

Ahmed Askora

Keyword(s):

Staphylococcus Aureus ◽

Special Focus ◽

Gram Positive ◽

First Time

Download Full-text

Advantages of Hyaluronic Acid and Its Combination with Other Bioactive Ingredients in Cosmeceuticals

Molecules ◽

10.3390/molecules26154429 ◽

2021 ◽

Vol 26 (15) ◽

pp. 4429

Author(s):

Anca Maria Juncan ◽

Dana Georgiana Moisă ◽

Antonello Santini ◽

Claudiu Morgovan ◽

Luca-Liviu Rus ◽

...

Keyword(s):

Hyaluronic Acid ◽

Glucuronic Acid ◽

Biological Effects ◽

Biological Processes ◽

Cosmetic Products ◽

Aesthetic Medicine ◽

Cosmetic Formulations ◽

Other Substances ◽

Bioactive Ingredients ◽

Brand Portfolio

This study proposes a review on hyaluronic acid (HA) known as hyaluronan or hyaluronate and its derivates and their application in cosmetic formulations. HA is a glycosaminoglycan constituted from two disaccharides (N-acetylglucosamine and D-glucuronic acid), isolated initially from the vitreous humour of the eye, and subsequently discovered in different tissues or fluids (especially in the articular cartilage and the synovial fluid). It is ubiquitous in vertebrates, including humans, and it is involved in diverse biological processes, such as cell differentiation, embryological development, inflammation, wound healing, etc. HA has many qualities that recommend it over other substances used in skin regeneration, with moisturizing and anti-ageing effects. HA molecular weight influences its penetration into the skin and its biological activity. Considering that, nowadays, hyaluronic acid has a wide use and a multitude of applications (in ophthalmology, arthrology, pneumology, rhinology, aesthetic medicine, oncology, nutrition, and cosmetics), the present study describes the main aspects related to its use in cosmetology. The biological effect of HA on the skin level and its potential adverse effects are discussed. Some available cosmetic products containing HA have been identified from the brand portfolio of most known manufacturers and their composition was evaluated. Further, additional biological effects due to the other active ingredients (plant extracts, vitamins, amino acids, peptides, proteins, saccharides, probiotics, etc.) are presented, as well as a description of their possible toxic effects.

Download Full-text

Pancreatic cancer metastasis: Mutual regulation of cancer- and stroma-derived matrix metalloproteinases

Pancreatology ◽

10.1016/j.pan.2012.12.156 ◽

2013 ◽

Vol 13 (2) ◽

pp. e29-e30

Author(s):

H. Habisch ◽

S. Zhou ◽

M. Siech ◽

T. Seufferlein ◽

M. Bachem

Keyword(s):

Pancreatic Cancer ◽

Matrix Metalloproteinases ◽

Cancer Metastasis ◽

Mutual Regulation

Download Full-text

Bacterial resistance to beta-lactam antibiotics: crystal structure of beta-lactamase from Staphylococcus aureus PC1 at 2.5 A resolution

Science ◽

10.1126/science.3107125 ◽

1987 ◽

Vol 236 (4802) ◽

pp. 694-701 ◽

Cited By ~ 222

Author(s):

O Herzberg ◽

J Moult

Keyword(s):

Crystal Structure ◽

Staphylococcus Aureus ◽

Bacterial Resistance ◽

Beta Lactamase ◽

Beta Lactam ◽

Beta Lactam Antibiotics

Download Full-text

Azukisapogenol Triterpene Glycosides from Oxytropis chiliophylla Royle

Molecules ◽

10.3390/molecules23102448 ◽

2018 ◽

Vol 23 (10) ◽

pp. 2448

Author(s):

Jun Wang ◽

Hongshuai Yang ◽

Yang Liu ◽

Kelsang Norbo ◽

Kewu Zeng ◽

...

Keyword(s):

Methyl Ester ◽

Glucuronic Acid ◽

Acid Methyl Ester ◽

Triterpene Glycosides ◽

Raw 264.7 Cells ◽

No Production ◽

Acid Methyl ◽

Potent Inhibition ◽

New Compounds ◽

First Time

Eight azukisapogenol triterpene glycosides, including five new compounds, oxychiliotriterpenosides A–E (1–5), two new methyl glucuronide derivatives that proved to be artifacts, oxychiliotriterpenoside E-glucuronic acid methyl ester (6) and myrioside B-glucuronic acid methyl ester (7), and a known one, myrioside B (8), was isolated from the aerial part of Oxytropis chiliophylla Royle. Their structures were elucidated based on extensive spectroscopic analyses and chemical methods. Triterpene glycosides were first obtained from O. chiliophylla, and those containing a galactose unit (1, 2, 5 and 6) and diglucosidic or triglucosidic linkage at C-29 (1–4), were reported from Oxytropis species for the first time, which might be recognized as a chemotaxonomic feature of O. chiliophylla. All isolated compounds were evaluated for their anti-inflammatory activities against NO production using lipopolysaccharide (LPS)-induced RAW 264.7 cells, but no compounds showed potent inhibition on NO production.

Download Full-text

Superoxide Dismutase 2 is Necessary for Key Steps in the Transcoelomic Route of Ovarian Cancer Metastasis

Free Radical Biology and Medicine ◽

10.1016/j.freeradbiomed.2013.10.429 ◽

2013 ◽

Vol 65 ◽

pp. S20

Author(s):

Madhubhani LP Hemachandra ◽

Usawadee Dier ◽

Larissa M Uusitalo ◽

Donghui Shin ◽

Sarah a Engelberth ◽

...

Keyword(s):

Ovarian Cancer ◽

Superoxide Dismutase ◽

Cancer Metastasis ◽

Key Steps ◽

Superoxide Dismutase 2

Download Full-text

Finding of Agr Phase Variants in Staphylococcus aureus

mBio ◽

10.1128/mbio.00796-19 ◽

2019 ◽

Vol 10 (4) ◽

Cited By ~ 3

Author(s):

Vishal Gor ◽

Aya J. Takemura ◽

Masami Nishitani ◽

Masato Higashide ◽

Veronica Medrano Romero ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Virulence Factors ◽

Phase Variation ◽

Accessory Gene ◽

Content Type ◽

Accessory Gene Regulator ◽

Immune Mediated ◽

A Minor ◽

First Time ◽

Phase Variants

ABSTRACT Staphylococcus aureus is an important human pathogen whose success is largely attributed to its vast arsenal of virulence factors that facilitate its invasion into, and survival within, the human host. The expression of these virulence factors is controlled by the quorum sensing accessory gene regulator (Agr) system. However, a large proportion of clinical S. aureus isolates are consistently found to have a mutationally inactivated Agr system. These mutants have a survival advantage in the host but are considered irreversible mutants. Here we show, for the first time, that a fraction of Agr-negative mutants can revert their Agr activity. By serially passaging Agr-negative strains and screening for phenotypic reversion of hemolysis and subsequent sequencing, we identified two mutational events responsible for reversion: a genetic duplication plus inversion event and a poly(A) tract alteration. Additionally, we demonstrate that one clinical Agr-negative methicillin-resistant S. aureus (MRSA) isolate could reproducibly generate Agr-revertant colonies with a poly(A) tract genetic mechanism. We also show that these revertants activate their Agr system upon phagocytosis. We propose a model in which a minor fraction of Agr-negative S. aureus strains are phase variants that can revert their Agr activity and may act as a cryptic insurance strategy against host-mediated stress. IMPORTANCE Staphylococcus aureus is responsible for a broad range of infections. This pathogen has a vast arsenal of virulence factors at its disposal, but avirulent strains are frequently isolated as the cause of clinical infections. These isolates have a mutated agr locus and have been believed to have no evolutionary future. Here we show that a fraction of Agr-negative strains can repair their mutated agr locus with mechanisms resembling phase variation. The agr revertants sustain an Agr OFF state as long as they exist as a minority but can activate their Agr system upon phagocytosis. These revertant cells might function as a cryptic insurance strategy to survive immune-mediated host stress that arises during infection.

Download Full-text

CHEMICAL CONSTITUENTS AND BIOACTIVITY OF Codium amplivesiculatum SETCHELL N. L.GARDNER (CHLOROPHYTA; BRYOPSIDALES)

CICIMAR Oceánides ◽

10.37543/oceanides.v28i2.124 ◽

2013 ◽

Vol 28 (2) ◽

pp. 1

Author(s):

A. Marín -Álvarez ◽

J. I. Murrillo -Álvarez ◽

M. Muñoz -Ochoa ◽

G. M. Molina -Salinas

Keyword(s):

Staphylococcus Aureus ◽

Silica Gel ◽

Vibrio Parahaemolyticus ◽

Marine Alga ◽

Chemical Constituents ◽

Ethanol Extract ◽

Solvent Mixtures ◽

Bioactive Substances ◽

First Time ◽

Tuberculosis Activity

In search of bioactive substances from Mexican marine organisms, crude ethanol-extract from the marine alga Codium amplivesiculatum was fractionated in chromatographic columns of silica gel at 60 Å (230-400 mesh) using solvent mixtures of increasing polarity. All the fractions were submitted to antibacterial assays. The major metabolite from an anti-tuberculosis fraction (MIC = 100 μg mL–1) was purified and identified as 1-octodecanol (1). The anti-tuberculosis activity was attributed to 1 with bases in previous reports. In addition, clerosterol (2) was obtained by crystallization from an active fraction against Staphylococcus aureus and Vibrio parahaemolyticus (MIC = 125 and 250 μg mL–1, respectively). Both structures were established by interpretation and comparison of infrared and 1H NMR spectroscopic data. In contrast with other studies, 2 showed a non-significant cytotoxicity against the cell line PC-3 (% GI = 21.05 ± 0.3 at 50 μg mL–1). To our knowledge, these metabolites are reported for the first time from C. amplivesiculatum, and this is one of very rare reports of saturated long-chain alcohols isolated from chlorophytes. Constituyentes químicos y bioactividad de Codium amplivesiculatum Con el propósito de descubrir sustancias bioactivas a partir de organismos marinos encontrados en México, se fraccionó el extracto crudo etanólico de Codium amplivesiculatum en columnas cromatográficas de sílica gel 60 Å (230-400 de malla) utilizando mezclas de solventes de polaridad creciente. Todas las fracciones se sometieron a ensayos antibacterianos. El principal metabolito de la fracción activa antituberculosis (MIC = 100 μg mL-1), fue purificado e identificado como 1-octodecanol (1). La actividad antituberculosis, basada en reportes previos, se atribuyó al compuesto 1. Además, se obtuvo clerosterol (2) por cristalización de una fracción activa frente a Staphylococcus aureus y Vibrio parahaemolyticus (MIC = 125 y 250 μg mL-1, respectivamente). Las dos estructuras fueron inferidas mediante interpretación y comparación de datos obtenidos por espectroscopía de IR-ATR y 1H RMN. En contraste con otros estudios, el compuesto 2 mostró una citotoxicidad no significativa contra la línea celular PC-3 (% IC = 21.05 ± 0.3 a 50 μg mL–1). Hasta donde sabemos, estos metabolitos se reportan por primera vez en C. amplivesiculatum y 1-octadecanol es un reporte muy raro de alcohol de cadena larga aislado de clorofitas.

Download Full-text