Benzophenone Compounds, from a Marine-Derived Strain of the Fungus Pestalotiopsis neglecta, Inhibit Proliferation of Pancreatic Cancer Cells by Targeting the MEK/ERK Pathway
Abstract:Pancreatic cancer, which has an extremely poor prognosis, is one of the most fatal human cancers. Chemotherapy is the main palliative treatment for advanced cancer patients and also plays an indispensable role in postoperative treatments for surgical patients. Therefore, there is an urgent need to develop more innovative anticancer drugs to fight against this fatal disease.Here, we investigate the potential of benzophenone derivatives, obtained from a marine-derived strain of the fungus Pestalotiopsis neglecta… Show more
“…In particular, 266 and 268 were found to suppress cell proliferation and induce apoptosis in the low micromolar range of 7.6 and 7.2 μmol/L, respectively. [ 135 ] …”
Section: Marine Habitats For Microorganisms Producing Halogenated Com...mentioning
Comprehensive Summary
Natural products derived from marine microorganisms have been received great attention as a potential source of new compound entities for drug discovery. The unique marine environment brings us a large group of halogen‐containing natural products with abundant biological functionality and good drugability. Meanwhile, biosynthetically halogenated reactions are known as a significant strategy used to increase the pharmacological activities and pharmacokinetic properties of compounds. Given that a tremendous increase in the number of new halogenated compounds from marine microorganisms in the last five years, it is necessary to summarize these compounds with their diverse structures and promising bioactivities. In this review, we have summarized the chemistry, biosynthesis (related halogenases), and biological activity of a total of 316 naturally halogenated compounds from marine microorganisms covering the period of 2015 to May 2021. Those reviewed chlorinated and brominated compounds with the ratio of 9 : 1 were predominantly originated from 36 genera of fungi (62%) and 9 bacterial strains (38%) with cytotoxic, antibacterial, and enzyme inhibitory activities, structural types of which are polyketides (38%), alkaloids (27%), phenols (11%), and others. This review would provide a plenty variety of promising lead halogenated compounds for drug discovery and inspire the development of new pharmaceutical agents.
“…In particular, 266 and 268 were found to suppress cell proliferation and induce apoptosis in the low micromolar range of 7.6 and 7.2 μmol/L, respectively. [ 135 ] …”
Section: Marine Habitats For Microorganisms Producing Halogenated Com...mentioning
Comprehensive Summary
Natural products derived from marine microorganisms have been received great attention as a potential source of new compound entities for drug discovery. The unique marine environment brings us a large group of halogen‐containing natural products with abundant biological functionality and good drugability. Meanwhile, biosynthetically halogenated reactions are known as a significant strategy used to increase the pharmacological activities and pharmacokinetic properties of compounds. Given that a tremendous increase in the number of new halogenated compounds from marine microorganisms in the last five years, it is necessary to summarize these compounds with their diverse structures and promising bioactivities. In this review, we have summarized the chemistry, biosynthesis (related halogenases), and biological activity of a total of 316 naturally halogenated compounds from marine microorganisms covering the period of 2015 to May 2021. Those reviewed chlorinated and brominated compounds with the ratio of 9 : 1 were predominantly originated from 36 genera of fungi (62%) and 9 bacterial strains (38%) with cytotoxic, antibacterial, and enzyme inhibitory activities, structural types of which are polyketides (38%), alkaloids (27%), phenols (11%), and others. This review would provide a plenty variety of promising lead halogenated compounds for drug discovery and inspire the development of new pharmaceutical agents.
“…Six new alkenylated tetrahydropyran derivatives belonged to polyketides, designated as (12R,13R)-dihydroxylanomycinol (73), (12S,13S)-dihydroxylanomycinol (74), (12R,13S)-dihydroxylanomycinol (75) and (12S,13R)-dihydroxylanomycinol (76), (12S,13R)-N-acetyl-dihydroxylanomycin (77) and (12S,13S)-N-acetyl-dihydroxylanomycin (78), together with one related known compound lanomycinol (79), were isolated from Westerdykella dispersa (the South China Sea). Compounds 73-79 exhibited moderate antifungal activities selectively against agricultural pathogenic fungi Rhizoctorzia solani, Verticillium dahliae, Helminthosporium maydis, Fusarium tricinctum, F. oxysporum, Botryosphaeria dothidea, and Alternaria fragriae [52].…”
Section: Antifungal Activitymentioning
confidence: 99%
“…Isolated compounds suppressed pancreatic cancer cell line PANC-1 proliferation and induced apoptosis. An in silico study suggested that benzophenone derivatives could potentially inhibit MEK activity by binding to the allosteric pocket in MEK [77].…”
Marine sediments are characterized by intense degradation of sedimenting organic matter in the water column and near surface sediments, combined with characteristically low temperatures and elevated pressures. Fungi are less represented in the microbial communities of sediments than bacteria and archaea and their relationships are competitive. This results in wide variety of secondary metabolites produced by marine sediment-derived fungi both for environmental adaptation and for interspecies interactions. Earlier marine fungal metabolites were investigated mainly for their antibacterial and antifungal activities, but now also as anticancer and cytoprotective drug candidates. This review aims to describe low-molecular-weight secondary metabolites of marine sediment-derived fungi in the context of their biological activity and covers research articles published between January 2016 and November 2020.
“…Their application extends beyond the common PL techniques of binding-site and biological-interactome mapping, target identification and proteome profiling, and surface conjugation techniques amongst others. They are also found in natural products that have broad-spectrum biological effects such as anticancer, antiviral, antimicrobial, and anti-inflammatory effects [2,[19][20][21][22]. The phototoxicity of this class of bioactive natural products is a probable adverse effect that may limit the widespread utilization of this pharmacophore in drug design [23].…”
The use of light-activated chemical probes to study biological interactions was first discovered in the 1960s, and has since found many applications in studying diseases and gaining deeper insight into various cellular mechanisms involving protein–protein, protein–nucleic acid, protein–ligand (drug, probe), and protein–co-factor interactions, among others. This technique, often referred to as photoaffinity labelling, uses radical precursors that react almost instantaneously to yield spatial and temporal information about the nature of the interaction and the interacting partner(s). This review focuses on the recent advances in chemical biology in the use of benzophenones and diazirines, two of the most commonly known light-activatable radical precursors, with a focus on the last three years, and is intended to provide a solid understanding of their chemical and biological principles and their applications.
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