scholarly journals Molecules and Metabolites from Natural Products as Inhibitors of Biofilm in Candida spp. pathogens

2019 ◽  
Vol 19 (28) ◽  
pp. 2567-2578 ◽  
Author(s):  
Rajeev K. Singla ◽  
Ashok K. Dubey
Keyword(s):  
Natural Products ◽  
Mechanism Of Action ◽  
Functional Characterization ◽  
Streptococcus Thermophilus ◽  
Antifungal Drugs ◽  
Bioactive Molecules ◽  
Review Of The Literature ◽  
Candida Spp ◽  
Biofilm Inhibition

Background: Biofilm is a critical virulence factor associated with the strains of Candida spp. pathogens as it confers significant resistance to the pathogen against antifungal drugs. Methods: A systematic review of the literature was undertaken by focusing on natural products, which have been reported to inhibit biofilms produced by Candida spp. The databases explored were from PubMed and Google Scholar. The abstracts and full text of the manuscripts from the literature were analyzed and included if found significant. Results: Medicinal plants from the order Lamiales, Apiales, Asterales, Myrtales, Sapindales, Acorales, Poales and Laurales were reported to inhibit the biofilms formed by Candida spp. From the microbiological sources, lactobacilli, Streptomyces chrestomyceticus and Streptococcus thermophilus B had shown the strong biofilm inhibition potential. Further, the diverse nature of the compounds from classes like terpenoids, phenylpropanoid, alkaloids, flavonoids, polyphenol, naphthoquinone and saponin was found to be significant in inhibiting the biofilm of Candida spp. Conclusion: Natural products from both plant and microbial origins have proven themselves as a goldmine for isolating the potential biofilm inhibitors with a specific or multi-locus mechanism of action. Structural and functional characterization of the bioactive molecules from active extracts should be the next line of approach along with the thorough exploration of the mechanism of action for the already identified bioactive molecules.

scholarly journals Ribosomally derived lipopeptides containing distinct fatty acyl moieties

2022 ◽  
Vol 119 (3) ◽  
pp. e2113120119
Author(s):  
Florian Hubrich ◽  
Nina M. Bösch ◽  
Clara Chepkirui ◽  
Brandon I. Morinaka ◽  
Michael Rust ◽  
...  
Keyword(s):  
Natural Products ◽  
Cyclic Peptide ◽  
Fatty Acyl ◽  
Antifungal Drugs ◽  
Guided Discovery ◽  
Bacterial Phyla ◽  
Peptide Synthetases ◽  
Antibacterial And Antifungal ◽  
Microbial Natural Products

Lipopeptides represent a large group of microbial natural products that include important antibacterial and antifungal drugs and some of the most-powerful known biosurfactants. The vast majority of lipopeptides comprise cyclic peptide backbones N-terminally equipped with various fatty acyl moieties. The known compounds of this type are biosynthesized by nonribosomal peptide synthetases, giant enzyme complexes that assemble their products in a non–gene-encoded manner. Here, we report the genome-guided discovery of ribosomally derived, fatty-acylated lipopeptides, termed selidamides. Heterologous reconstitution of three pathways, two from cyanobacteria and one from an arctic, ocean-derived alphaproteobacterium, allowed structural characterization of the probable natural products and suggest that selidamides are widespread over various bacterial phyla. The identified representatives feature cyclic peptide moieties and fatty acyl units attached to (hydroxy)ornithine or lysine side chains by maturases of the GCN5-related N-acetyltransferase superfamily. In contrast to nonribosomal lipopeptides that are usually produced as congener mixtures, the three selidamides are selectively fatty acylated with C10, C12, or C16 fatty acids, respectively. These results highlight the ability of ribosomal pathways to emulate products with diverse, nonribosomal-like features and add to the biocatalytic toolbox for peptide drug improvement and targeted discovery.

scholarly journals Pharmacological Developments Obtained from Marine Natural Products and Current Pipeline Perspective

2011 ◽  
Vol 6 (2) ◽  
pp. 1934578X1100600
Author(s):  
Galeano J. Elkin ◽  
Jhon J. Rojas ◽  
Alejandro Martínez
Keyword(s):  
Natural Products ◽  
Side Effects ◽  
Drug Development ◽  
Mechanism Of Action ◽  
Marine Organisms ◽  
Bioactive Molecules ◽  
Phase Iii ◽  
New Drug Development ◽  
Therapeutic Alternatives ◽  
Positive Results

Marine organisms represent a new extensive source for bioactive molecules. They have the potential to provide new therapeutic alternatives to treat human diseases. In this paper, we describe and discuss a variety of isolated and semisynthetic molecules obtained from marine sources. These compounds are in phase II, phase III and at the commercialization stage of new drug development. A description of the mechanism of action, dosage used and side effects are also reported. The positive results obtained from these studies have triggered the development of new studies to evaluate the prospects for utilization of marine organisms.

scholarly journals Medium-Length Lipids Facilitate Cell-Permeability and Bioactivity

2021 ◽  
Author(s):  
Johannes Morstein ◽  
Alice Capecchi ◽  
Konstantin Hinnah ◽  
Jerome Petit-Jacques ◽  
Jean-Louis Reymond ◽  
...  
Keyword(s):  
Natural Products ◽  
Small Molecules ◽  
Mammalian Cells ◽  
Bioactive Molecules ◽  
Cell Permeability ◽  
Probe Design ◽  
Medium Length ◽  
Intracellular Targets ◽  
Powerful Strategy

The majority of bioactive molecules act on membrane proteins or intracellular targets and therefore needs to partition into or cross biological membranes. Natural products often exhibit lipid modifications to facilitate critical molecule-membrane interactions and in many cases their bioactivity is markedly reduced upon removal of a lipid group. However, despite its importance in nature, lipid-conjugation of small molecules is not commonly used in chemical biology and medicinal chemistry, and the effect of such conjugation has not been systematically studied. To understand the composition of lipids found in natural products, we carried out a chemoinformatic characterization of the ‘natural product lipidome’. According to this analysis, lipidated natural products predominantly contain saturated linear medium-length lipids, which are significantly shorter than those found in membranes and lipidated proteins. To study the usefulness of such modifications in probe design, we systematically explored the effect of lipid conjugation on five different small molecule chemotypes and find that permeability, cellular retention, subcellular localization, and bioactivity can be significantly modulated depending on the type of lipid tail used. We demonstrate that medium-length lipid tails can render impermeable molecules cell-permeable and switch on their bioactivity. Saturated medium-length lipids (e.g. C10) are found to be ideal for the bioactivity of small molecules in mammalian cells, while saturated long-chain lipids (e.g. C18) often significantly reduce bioavailability and activity. Together, our findings suggest that conjugation of small molecules with medium-length lipids could be a powerful strategy for the design of probes and drugs.

scholarly journals Structural and functional characterization of C0021158, a high-affinity monoclonal antibody that inhibits Arginase 2 function via a novel non-competitive mechanism of action

mAbs ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 1801230
Author(s):  
Mark Austin ◽  
Daniel Burschowsky ◽  
Denice T.Y. Chan ◽  
Lesley Jenkinson ◽  
Stuart Haynes ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Mechanism Of Action ◽  
Functional Characterization ◽  
High Affinity ◽  
Competitive Mechanism

scholarly journals Asymmetric Alkene and Arene Halofunctionalization Reactions in Meroterpenoid Biosynthesis

Synlett ◽  
2017 ◽  
Vol 29 (04) ◽  
pp. 401-409 ◽  
Author(s):  
Bradley Moore
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Bioactive Molecules ◽  
Broad Distribution ◽  
Rearrangement Reactions

Meroterpenoid natural products are important bioactive molecules with broad distribution throughout nature. In Streptomyces bacteria, naphthoquinone-based meroterpenoids comprise a simple yet structurally fascinating group of natural product antibiotics that are enzymatically constructed through a series of asymmetric alkene and arene halofunctionalization reactions. This account article highlights our discovery and characterization of a group of vanadium-dependent chloroperoxidase enzymes that catalyze halogen-assisted cyclization and rearrangement reactions and have inspired biomimetic syntheses of numerous meroterpenoid natural products.1 Introduction2 Early Biosynthetic Insights and the Characterization of Alkene Halofunctionalization in Napyradiomycin Biosynthesis3 Discovery of the Merochlorin Natural Products and Enzymatic Aryl Halofunctionalization4 Discovery and Development of Unifying THN-Based Meroterpenoid Biosynthesis and Synthesis Approaches5 Insights into Naphterpin and Marinone Biosynthesis Involving Cryptic Aryl Halofunctionalization Reactions6 Closing Thoughts

Emerging Marine Immunomodulatory Small-molecules (2010- Present)

2019 ◽  
Vol 13 (3) ◽  
pp. 187-196
Author(s):  
Ran Li ◽  
Yu-Cheng Gu ◽  
Wen Zhang
Keyword(s):  
Natural Products ◽  
Small Molecules ◽  
Mechanism Of Action ◽  
Marine Natural Products ◽  
Bioactive Molecules ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Unique Source

Background: Immunomodulation-based therapy has achieved a breakthrough in the last decade, which stimulates the passion of searching for potential immunomodulatory substances in recent years. Objective: Marine natural products are a unique source of immunomodulatory substances. This paper summarized the emerging marine natural small-molecules and related synthesized derivatives with immunomodulatory activities to provide readers an overview of these bioactive molecules and their potential in immunomodulation therapy. Conclusion: An increasing number of immunomodulatory marine small-molecules with diverse intriguing structure-skeletons were discovered. They may serve as a basis for further studies of marine natural products for their chemistry, related mechanism of action and structure- activity relationships.

scholarly journals (R)-(+)-β-Citronellol and (S)-(−)-β-Citronellol in Combination with Amphotericin B against Candida Spp.

2020 ◽  
Vol 21 (5) ◽  
pp. 1785 ◽  
Author(s):  
Daniele Silva ◽  
Hermes Diniz-Neto ◽  
Laísa Cordeiro ◽  
Maria Silva-Neta ◽  
Shellygton Silva ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Minimum Inhibitory Concentration ◽  
Amphotericin B ◽  
Mechanism Of Action ◽  
Inhibitory Concentration ◽  
Association Studies ◽  
Antifungal Drugs ◽  
Candida Spp ◽  
Fungal Cell

The enantiomers (R)-(+)-β-citronellol and (S)-(−)-β-citronellol are present in many medicinal plants, but little is understood about their bioactivity against Candida yeasts. This study aimed to evaluate the behavior of positive and negative enantiomers of β-citronellol on strains of Candida albicans and C. tropicalis involved in candidemia. The minimum inhibitory concentration (MIC) and minimum fungicide concentration (MFC) were determined. The evaluation of growth kinetics, mechanism of action, and association studies with Amphotericin B (AB) using the checkerboard method was also performed. R-(+)-β-citronellol and S-(−)-β-citronellol presented a MIC50% of 64 µg/mL and a MFC50% of 256 µg/mL for C. albicans strains. For C. tropicalis, the isomers exhibited a MIC50% of 256 µg/mL and a MFC50% of 1024 µg/mL. In the mechanism of action assay, both substances displayed an effect on the fungal membrane but not on the fungal cell wall. Synergism and indifference were observed in the association of R-(+)-β-citronellol and AB, while the association between S-(−)-β-citronellol and AB displayed synergism, additivity, and indifference. In conclusion, both isomers of β-citronellol presented a similar profile of antifungal activity. Hence, they can be contemplated in the development of new antifungal drugs providing that further research is conducted about their pharmacology and toxicity.

scholarly journals Antifungal Activity and Mechanism of Action of Different Parts of Myrtus communis Growing in Saudi Arabia against Candida Spp.

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Abdullah A. Alyousef
Keyword(s):  
Saudi Arabia ◽  
Natural Products ◽  
Antifungal Activity ◽  
Candida Glabrata ◽  
Candida Parapsilosis ◽  
Antifungal Drugs ◽  
Root Extract ◽  
Myrtus Communis ◽  
Leaf Extracts ◽  
Candida Spp

Discovering new antifungal drugs from natural products is a key target for the treatment of infections, such as candidiasis and other Candida-related infections. As current therapeutic drugs for the treatment of infections, such as candidiasis and other Candida-related infections, have adverse effects on human health, discovering new antifungal drugs from natural products is urgently needed. The objective of this study was to evaluate the antifungal activity of the methanolic and sodium phosphate buffer extracts derived from various parts of Myrtus communis, a plant that is traditionally used in Saudi Arabia, against Candida albicans (ATCC 10213), Candida glabrata (ATCC 2001), Candida kefyr (ATCC 66028), Candida parapsilosis (ATCC 22019), and Candida tropicalis (ATCC 750). A well diffusion assay was performed to assess the antifungal activity through the measurement of the zone of inhibition. Of the extracts, those extracted with methanol from the roots and leaves displayed strong inhibitory activity against Candida glabrata ( 23.5 ± 0.12 and 20.7 ± 0.22 , respectively), at 50 mg/ml, with 5 mg/ml fluconazole administered as the standard control. The minimal inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) values were 12.5 mg/ml and 25 mg/ml for the M. communis root extract and 25 mg/ml and 50 mg/ml for the M. communis leaf extract against Candida glabrata. The results were confirmed by scanning electron microscopy (SEM) imaging of the control and treated strains of Candida glabrata. Based on SEM, these extracts could alter the morphology and cause loss of cell integrity. The effect of M. communis root and leaf extracts on Candida cells was also determined by measuring the absorbance at 260 nm after treatment for 1 h at 37°C. Interestingly, the 260 nm absorbing material was higher in Candida glabrata than in the resistant strain, Candida parapsilosis (ATCC 22019). Based on our findings, the crude methanolic extract of M. communis roots and leaves exhibited good antifungal activity against the Candida glabrata strain. SEM results and estimation of the 260 nm absorbance material proved that the extract might act on the cell wall and cell membrane of Candida cells, further leading to cell death.

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