HIV-1 Integrase Inhibition Activity by Spiroketals Derived from Plagius flosculosus, an Endemic Plant of Sardinia (Italy) and Corsica (France)

In this work we investigated, for the first time, the effect of Plagius flosculosus (L.) Alavi & Heywood, a Sardinian–Corsican endemic plant, on HIV-1 integrase (IN) activity. The phytochemical analysis of the leaves chloroform extract led us to isolate and characterize three compounds (SPK1, SPK2, and SPK3) belonging to the spiroketals, a group of naturally occurring metabolites of phytochemical relevance with interesting biological properties. Due to their structural diversity, these cyclic ketals have attracted the interest of chemists and biologists. SPK1, SPK2, and SPK3 were evaluated here for their ability to inhibit HIV-1 integrase activity in biochemical assays. The results showed that all the compounds inhibited HIV-1 IN activity. In particular, the most active one was SPK3, which interfered in a low molecular range (IC50 of 1.46 ± 0.16 µM) with HIV-1 IN activity in the presence/absence of the LEDGF cellular cofactor. To investigate the mechanism of action, the three spiroketals were also tested on HIV-1 RT-associated Ribonuclease H (RNase H) activity, proving to be active in inhibiting this function. Although SPK3 was unable to inhibit viral replication in cell culture, it promoted the IN multimerization. We hypothesize that SPK3 inhibited HIV-1 IN through an allosteric mechanism of action

Recent Advances in Natural Product-Based Anti-Biofilm Approaches to Control Infections

Bacterial biofilms are highly organized surface-associated communities of bacteria encased within an extracellular matrix produced by themselves, capable of growing in connection with different biological or inert surfaces such as artificial joints or catheters. Biofilms are commonly associated with many health problems, such as endocarditis, otitis media, periodontitis, prostatitis, and urinary tract infections. Several bacteria, such as Escherichia coli, Staphylococcus aureus, Streptococcus mutans, and Pseudomonas aeruginosa, or fungal pathogen as Candida albicans, can form biofilms in the body tissues, leading to different infections. The inherently defensive character of the biofilm is demonstrated by enhanced persistence of bacteria grown in the sessile mode respect to bacteria grown planktonically. This makes most biofilm- associated infections difficult to eradicate, thus contributing to disease chronicity. Since natural products provide a diverse array of chemical structures and possess a wide variety of biological properties, natural resources are worldwide exploited in the search of new pharmaceuticals. In this context bioactive secondary metabolites from natural sources, useful for the new antimicrobial and anti-biofilm drugs, are of interest. In this review, the role of small molecules from plants and marine organisms in inhibiting and/or dispersing bacterial biofilms is discussed, as well as the approaches that have been applied to the discovery of lead small molecules that mediate biofilm development. Molecules inhibiting the formation of biofilm may have therapeutic potential. Several candidates, as halogenated furanones, 2-amminoimidazole alkaloids and flavonoids have been already isolated and characterized from many plants and from marine organisms. - See more at: http://www.eurekaselect.com/127277/article#sthash.615dJ78t.dpu

Plant Derived Natural Products against Pseudomonas aeruginosa and Staphylococcus aureus: Antibiofilm Activity and Molecular Mechanisms

Bacteria are social organisms able to build complex structures, such as biofilms, that are highly organized surface-associated communities of microorganisms, encased within a self- produced extracellular matrix. Biofilm is commonly associated with many health problems since its formation increases resistance to antibiotics and antimicrobial agents, as in the case of Pseudomonas aeruginosa and Staphylococcus aureus, two human pathogens causing major concern. P. aeruginosa is responsible for severe nosocomial infections, the most frequent of which is ventilator-associated pneumonia, while S. aureus causes several problems, like skin infections, septic arthritis, and endocarditis, to name just a few. Literature data suggest that natural products from plants, bacteria, fungi, and marine organisms have proven to be effective as anti-biofilm agents, inhibiting the formation of the polymer matrix, suppressing cell adhesion and attachment, and decreasing the virulence factors’ production, thereby blocking the quorum sensing network. Here, we focus on plant derived chemicals, and provide an updated literature review on the anti-biofilm properties of terpenes, flavonoids, alkaloids, and phenolic compounds. Moreover, whenever information is available, we also report the mechanisms of actio

Chemical Fractionation Joint to In-Mixture NMR Analysis for Avoiding the Hepatotoxicity of Teucrium chamaedrys L. subsp. chamaedrys

Dietary supplements based on Teucrium chamaedrys L. subsp. chamaedrys aerial parts were banned, due to the hepatotoxicity of furan-containing neo-clerodane constituents. Indeed, the plant leaf content in phenolic compounds could be further exploited for their antioxidant capability. Accordingly, bio-guided fractionation strategies have been applied, obtaining seven partially purified extracts. These latter were chemically investigated through 1D and 2D NMR techniques and tested for their antiradical, reducing and cytotoxic capability. Data acquired highlighted that, through a simple phytochemical approach, a progressive neo-clerodane depletion occurred, while maximizing phenylethanoid glycosides in alcoholic fractions. Thus, although the plant cannot be used as a botanical remedy as such, it is suggested as a source of healthy compounds, pure or in mixture, to be handled in pharmaceutical, nutraceutical and/or cosmeceutical sectors

NMR-Based Plant Metabolomics in Nutraceutical Research: An Overview

Few topics are able to channel the interest of researchers, the public, and industries, like nutraceuticals. The ever-increasing demand of new compounds or new sources of known active compounds, along with the need of a better knowledge about their effectiveness, mode of action, safety, etc., led to a significant effort towards the development of analytical approaches able to answer the many questions related to this topic. Therefore, the application of cutting edges approaches to this area has been observed. Among these approaches, metabolomics is a key player. Herewith, the applications of NMR-based metabolomics to nutraceutical research are discussed: after a brief overview of the analytical workflow, the use of NMR-based metabolomics to the search for new compounds or new sources of known nutraceuticals are reviewed. Then, possible applications for quality control and nutraceutical optimization are suggested. Finally, the use of NMR-based metabolomics to study the impact of nutraceuticals on human metabolism is discussed

Phytochemical Investigation of Myrcianthes cisplatensis: Structural Characterization of New p-Coumaroyl Alkylphloroglucinols and Antimicrobial Evaluation Against Staphylococcus aureus

Species of Myrtaceae Juss., the ninth largest family of flowering plants, are a valuable source of bioactive specialized metabolites. A leading position belongs to phloroglucinol derivatives, thanks to their unusual structural features and biological and pharmacological properties. Myrcianthes cisplatensis (Cambess.) O. Berg, a common tree on the banks of rivers and streams of Uruguay, southern Brazil, and northern Argentina, with aromatic leaves, is known as a diuretic, febrifuge, tonic, and good remedy for lung and bronchial diseases. Despite knowledge about traditional use, few data on its phytochemical properties have been reported in the literature. The methanol extract of M. cisplatensis, grown in Arizona, USA, was first partitioned between dichloromethane and water and then with ethyl acetate. The enriched fractions were evaluated using a broth microdilution assay against Staphylococcus aureus ATCC 29213 and 43300 (methicillin-resistant S. aureus (MRSA)). The potential antimicrobial activity seemed to increase in the dichloromethane extract, with a MIC value of 16 µg/mL against both strains. Following a bio-guided approach, chromatographic techniques allowed for isolating three coumarin derivatives, namely endoperoxide G3, catechin, and quercitrin, and four new p-coumaroyl alkylphloroglucinol glucosides, named p-coumaroylmyrciacommulone A-D. Their structures were characterized through spectroscopic techniques: 2D-NMR experiments (HSQC, HMBC, and HSQC-TOCSY) and spectrometric analyses (HR-MS). The antimicrobial assessment of pure compounds against S. aureus ATCC 29213 and ATCC 43300 demonstrated the best activity for p-coumaroylmyrciacommulone C and D with the growth inhibition of 50% at 32 µg/mL against both strains of S. aureus

NMR Profiling of Ononis diffusa Identifies Cytotoxic Compounds against Cetuximab-Resistant Colon Cancer Cell Lines

In the search of new natural products to be explored as possible anticancer drugs, two plant species, namely Ononis diffusa and Ononis variegata, were screened against colorectal cancer cell lines. The cytotoxic activity of the crude extracts was tested on a panel of colon cancer cell models including cetuximab-sensitive (Caco-2, GEO, SW48), intrinsic (HT-29 and HCT-116), and acquired (GEO-CR, SW48-CR) cetuximab-resistant cell lines. Ononis diffusa showed remarkable cytotoxic activity, especially on the cetuximab-resistant cell lines. The active extract composition was determined by NMR analysis. Given its complexity, a partial purification was then carried out. The fractions obtained were again tested for their biological activity and their metabolite content was determined by 1D and 2D NMR analysis. The study led to the identification of a fraction enriched in oxylipins that showed a 92% growth inhibition of the HT-29 cell line at a concentration of 50 µg/mL

Phloroglucinols from Myrtaceae: attractive targets for structural characterization, biological properties and synthetic procedures

Myrtaceae Juss. is a very large family of flowering plants, that are a valuable source of bioactive compounds. From the phytochemical point of view, apart from ubiquitous tannins, flavonoid derivatives and volatile oils, Myrtaceae plants are very rich in phloroglucinol derivatives, divided in two principal subclasses: oligomeric acylphloroglucinols and phloroglucinol-terpene adducts. Despite this large structural variability, many studies on phloroglucinols from the Myrtaceae have focused on unique bioactive acylphloroglucinol compounds, named myrtucommulones. Nevertheless, many studies also reported other interesting phloroglucinol derivatives. Therefore, in this review, a comprehensive description of the chemical features of acylphloroglucinols and meroterpenoid-acylphloroglucinols from the Myrtaceae family is presented along with their biological activities. Moreover, since myrtucommulones and their derivatives have become attractive targets for organic chemists, thanks to their structural features and biological activities, relevant approaches and synthetic procedures are herewith discusse