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Mar. Drugs, Volume 12, Issue 2 (February 2014), Pages 568-1168

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Open AccessEditorial Acknowledgement to Reviewers of Marine Drugs in 2013
Mar. Drugs 2014, 12(2), 1160-1168; https://doi.org/10.3390/md12021160
Received: 20 February 2014 / Accepted: 24 February 2014 / Published: 24 February 2014
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Abstract
The editors of Marine Drugs would like to express their sincere gratitude to the following reviewers for assessing manuscripts in 2013 [...] Full article
Open AccessEditorial Marine Drugs Best Paper Award 2014
Mar. Drugs 2014, 12(2), 1157-1159; https://doi.org/10.3390/md12021157
Received: 27 January 2014 / Accepted: 13 February 2014 / Published: 21 February 2014
Cited by 1 | PDF Full-text (354 KB) | HTML Full-text | XML Full-text
Abstract
Marine Drugs initiated a “Best Paper Award” in 2013 [1] to recognize outstanding papers published in our journal in the area of research, development and production of drugs from the sea, including marine natural product chemistry. We are pleased to announce the second
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Marine Drugs initiated a “Best Paper Award” in 2013 [1] to recognize outstanding papers published in our journal in the area of research, development and production of drugs from the sea, including marine natural product chemistry. We are pleased to announce the second “Marine Drugs Best Paper Award” for 2014. Nominations were selected by the Editor-in-Chief, Associate Editors and Editorial Board Members of Marine Drugs from all papers published in 2010; reviews and articles being evaluated separately. [...] Full article
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Open AccessArticle Krempfielins N–P, New Anti-Inflammatory Eunicellins from a Taiwanese Soft Coral Cladiella krempfi
Mar. Drugs 2014, 12(2), 1148-1156; https://doi.org/10.3390/md12021148
Received: 11 December 2013 / Revised: 22 January 2014 / Accepted: 7 February 2014 / Published: 21 February 2014
Cited by 10 | PDF Full-text (869 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Three new eunicellin-type diterpenoids, krempfielins N–P (13), were isolated from a Taiwanese soft coral Cladiella krempfi. The structures of the new metabolites were elucidated by extensive spectroscopic analysis and by comparison with spectroscopic data of related known compounds.
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Three new eunicellin-type diterpenoids, krempfielins N–P (13), were isolated from a Taiwanese soft coral Cladiella krempfi. The structures of the new metabolites were elucidated by extensive spectroscopic analysis and by comparison with spectroscopic data of related known compounds. Compound 3 exhibited activity to inhibit superoxide anion generation. Both 1 and 3, in particular 1, were shown to display significant anti-inflammatory activity by inhibiting the elastase release in FMLP/CB-induced human neutrophils. Full article
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Open AccessArticle The Marine Sponge-Derived Inorganic Polymers, Biosilica and Polyphosphate, as Morphogenetically Active Matrices/Scaffolds for the Differentiation of Human Multipotent Stromal Cells: Potential Application in 3D Printing and Distraction Osteogenesis
Mar. Drugs 2014, 12(2), 1131-1147; https://doi.org/10.3390/md12021131
Received: 28 November 2013 / Revised: 10 January 2014 / Accepted: 17 February 2014 / Published: 21 February 2014
Cited by 30 | PDF Full-text (1300 KB) | HTML Full-text | XML Full-text
Abstract
The two marine inorganic polymers, biosilica (BS), enzymatically synthesized from ortho-silicate, and polyphosphate (polyP), a likewise enzymatically synthesized polymer consisting of 10 to >100 phosphate residues linked by high-energy phosphoanhydride bonds, have previously been shown to display a morphogenetic effect on osteoblasts. In
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The two marine inorganic polymers, biosilica (BS), enzymatically synthesized from ortho-silicate, and polyphosphate (polyP), a likewise enzymatically synthesized polymer consisting of 10 to >100 phosphate residues linked by high-energy phosphoanhydride bonds, have previously been shown to display a morphogenetic effect on osteoblasts. In the present study, the effect of these polymers on the differential differentiation of human multipotent stromal cells (hMSC), mesenchymal stem cells, that had been encapsulated into beads of the biocompatible plant polymer alginate, was studied. The differentiation of the hMSCs in the alginate beads was directed either to the osteogenic cell lineage by exposure to an osteogenic medium (mineralization activation cocktail; differentiation into osteoblasts) or to the chondrogenic cell lineage by incubating in chondrocyte differentiation medium (triggering chondrocyte maturation). Both biosilica and polyP, applied as Ca2+ salts, were found to induce an increased mineralization in osteogenic cells; these inorganic polymers display also morphogenetic potential. The effects were substantiated by gene expression studies, which revealed that biosilica and polyP strongly and significantly increase the expression of bone morphogenetic protein 2 (BMP-2) and alkaline phosphatase (ALP) in osteogenic cells, which was significantly more pronounced in osteogenic versus chondrogenic cells. A differential effect of the two polymers was seen on the expression of the two collagen types, I and II. While collagen Type I is highly expressed in osteogenic cells, but not in chondrogenic cells after exposure to biosilica or polyP, the upregulation of the steady-state level of collagen Type II transcripts in chondrogenic cells is comparably stronger than in osteogenic cells. It is concluded that the two polymers, biosilica and polyP, are morphogenetically active additives for the otherwise biologically inert alginate polymer. It is proposed that alginate, supplemented with polyP and/or biosilica, is a suitable biomaterial that promotes the growth and differentiation of hMSCs and might be beneficial for application in 3D tissue printing of hMSCs and for the delivery of hMSCs in fractures, surgically created during distraction osteogenesis. Full article
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Open AccessArticle Tanjungides A and B: New Antitumoral Bromoindole Derived Compounds from Diazona cf formosa. Isolation and Total Synthesis
Mar. Drugs 2014, 12(2), 1116-1130; https://doi.org/10.3390/md12021116
Received: 2 December 2013 / Revised: 16 December 2013 / Accepted: 24 January 2014 / Published: 21 February 2014
Cited by 6 | PDF Full-text (961 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Tanjungides A (1) (Z isomer) and B (2) (E isomer), two novel dibrominated indole enamides, have been isolated from the tunicate Diazona cf formosa. Their structures were determined by spectroscopic methods including HRMS, and extensive 1D
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Tanjungides A (1) (Z isomer) and B (2) (E isomer), two novel dibrominated indole enamides, have been isolated from the tunicate Diazona cf formosa. Their structures were determined by spectroscopic methods including HRMS, and extensive 1D and 2D NMR. The stereochemistry of the cyclised cystine present in both compounds was determined by Marfey’s analysis after chemical degradation and hydrolysis. We also report the first total synthesis of these compounds using methyl 1H-indole-3-carboxylate as starting material and a linear sequence of 11 chemical steps. Tanjungides A and B exhibit significant cytotoxicity against human tumor cell lines. Full article
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Open AccessArticle Mode of Action of Diterpene and Characterization of Related Metabolites from the Soft Coral, Xenia elongata
Mar. Drugs 2014, 12(2), 1102-1115; https://doi.org/10.3390/md12021102
Received: 9 December 2013 / Revised: 25 January 2014 / Accepted: 27 January 2014 / Published: 20 February 2014
Cited by 7 | PDF Full-text (1100 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Chemical and biological investigation of the cultured marine soft coral Xenia elongata led to the isolation of two new diterpenes (2, 3). Their structures were elucidated using a combination of NMR and mass spectrometry. Biological evaluations and assessments were determined
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Chemical and biological investigation of the cultured marine soft coral Xenia elongata led to the isolation of two new diterpenes (2, 3). Their structures were elucidated using a combination of NMR and mass spectrometry. Biological evaluations and assessments were determined using the specific apoptosis induction assay based on genetically engineered mammalian cell line D3 deficient in Bak and Bax and derived from a mouse epithelial cell. The diterpenes induce apoptosis in low micromolar concentrations. The results indicate that the previously isolated compound (1) affects cell in a manner similar to that of HSP90 and HDAC inhibitors and in a manner opposite of PI3 kinase/mTOR inhibitors. Compound (3) inhibits selectively HDAC6 in high micromolar concentrations. Full article
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Open AccessReview Marketed Marine Natural Products in the Pharmaceutical and Cosmeceutical Industries: Tips for Success
Mar. Drugs 2014, 12(2), 1066-1101; https://doi.org/10.3390/md12021066
Received: 2 December 2013 / Revised: 14 January 2014 / Accepted: 27 January 2014 / Published: 17 February 2014
Cited by 118 | PDF Full-text (723 KB) | HTML Full-text | XML Full-text
Abstract
The marine environment harbors a number of macro and micro organisms that have developed unique metabolic abilities to ensure their survival in diverse and hostile habitats, resulting in the biosynthesis of an array of secondary metabolites with specific activities. Several of these metabolites
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The marine environment harbors a number of macro and micro organisms that have developed unique metabolic abilities to ensure their survival in diverse and hostile habitats, resulting in the biosynthesis of an array of secondary metabolites with specific activities. Several of these metabolites are high-value commercial products for the pharmaceutical and cosmeceutical industries. The aim of this review is to outline the paths of marine natural products discovery and development, with a special focus on the compounds that successfully reached the market and particularly looking at the approaches tackled by the pharmaceutical and cosmetic companies that succeeded in marketing those products. The main challenges faced during marine bioactives discovery and development programs were analyzed and grouped in three categories: biodiversity (accessibility to marine resources and efficient screening), supply and technical (sustainable production of the bioactives and knowledge of the mechanism of action) and market (processes, costs, partnerships and marketing). Tips to surpass these challenges are given in order to improve the market entry success rates of highly promising marine bioactives in the current pipelines, highlighting what can be learned from the successful and unsuccessful stories that can be applied to novel and/or ongoing marine natural products discovery and development programs. Full article
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Open AccessReview Co-Cultivation—A Powerful Emerging Tool for Enhancing the Chemical Diversity of Microorganisms
Mar. Drugs 2014, 12(2), 1043-1065; https://doi.org/10.3390/md12021043
Received: 9 January 2014 / Revised: 23 January 2014 / Accepted: 6 February 2014 / Published: 17 February 2014
Cited by 78 | PDF Full-text (779 KB) | HTML Full-text | XML Full-text
Abstract
Marine-derived bacteria and fungi are promising sources of novel bioactive compounds that are important for drug discovery programs. However, as encountered in terrestrial microorganisms there is a high rate of redundancy that results in the frequent re-discovery of known compounds. Apparently only a
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Marine-derived bacteria and fungi are promising sources of novel bioactive compounds that are important for drug discovery programs. However, as encountered in terrestrial microorganisms there is a high rate of redundancy that results in the frequent re-discovery of known compounds. Apparently only a part of the biosynthetic genes that are harbored by fungi and bacteria are transcribed under routine laboratory conditions which involve cultivation of axenic microbial strains. Many biosynthetic genes remain silent and are not expressed in vitro thereby seriously limiting the chemical diversity of microbial compounds that can be obtained through fermentation. In contrast to this, co-cultivation (also called mixed fermentation) of two or more different microorganisms tries to mimic the ecological situation where microorganisms always co-exist within complex microbial communities. The competition or antagonism experienced during co-cultivation is shown to lead to a significantly enhanced production of constitutively present compounds and/or to an accumulation of cryptic compounds that are not detected in axenic cultures of the producing strain. This review highlights the power of co-cultivation for increasing the chemical diversity of bacteria and fungi drawing on published studies from the marine and from the terrestrial habitat alike. Full article
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Open AccessReview The Lipopolysaccharide Export Pathway in Escherichia coli: Structure, Organization and Regulated Assembly of the Lpt Machinery
Mar. Drugs 2014, 12(2), 1023-1042; https://doi.org/10.3390/md12021023
Received: 15 January 2014 / Revised: 22 January 2014 / Accepted: 28 January 2014 / Published: 17 February 2014
Cited by 18 | PDF Full-text (862 KB) | HTML Full-text | XML Full-text
Abstract
The bacterial outer membrane (OM) is a peculiar biological structure with a unique composition that contributes significantly to the fitness of Gram-negative bacteria in hostile environments. OM components are all synthesized in the cytosol and must, then, be transported efficiently across three compartments
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The bacterial outer membrane (OM) is a peculiar biological structure with a unique composition that contributes significantly to the fitness of Gram-negative bacteria in hostile environments. OM components are all synthesized in the cytosol and must, then, be transported efficiently across three compartments to the cell surface. Lipopolysaccharide (LPS) is a unique glycolipid that paves the outer leaflet of the OM. Transport of this complex molecule poses several problems to the cells due to its amphipatic nature. In this review, the multiprotein machinery devoted to LPS transport to the OM is discussed together with the challenges associated with this process and the solutions that cells have evolved to address the problem of LPS biogenesis. Full article
(This article belongs to the Special Issue Marine Lipopolysaccharides)
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Open AccessArticle Solwaric Acids A and B, Antibacterial Aromatic Acids from a Marine Solwaraspora sp.
Mar. Drugs 2014, 12(2), 1013-1022; https://doi.org/10.3390/md12021013
Received: 19 December 2013 / Revised: 24 January 2014 / Accepted: 24 January 2014 / Published: 14 February 2014
Cited by 16 | PDF Full-text (563 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Two novel trialkyl-substituted aromatic acids, solwaric acids A and B, were isolated from a marine Solwaraspora sp. cultivated from the ascidian Trididemnum orbiculatum. Solwaric acids A and B were isotopically labeled with U-13C glucose, and analysis of a 13C–
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Two novel trialkyl-substituted aromatic acids, solwaric acids A and B, were isolated from a marine Solwaraspora sp. cultivated from the ascidian Trididemnum orbiculatum. Solwaric acids A and B were isotopically labeled with U-13C glucose, and analysis of a 13C–13C COSY allowed for unambiguous determination of the location of the phenyl methyl group. The two novel compounds demonstrated antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA). Full article
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Open AccessArticle Butremycin, the 3-Hydroxyl Derivative of Ikarugamycin and a Protonated Aromatic Tautomer of 5′-Methylthioinosine from a Ghanaian Micromonospora sp. K310
Mar. Drugs 2014, 12(2), 999-1012; https://doi.org/10.3390/md12020999
Received: 22 November 2013 / Revised: 24 December 2013 / Accepted: 21 January 2014 / Published: 14 February 2014
Cited by 19 | PDF Full-text (436 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A new actinomycete strain Micromonospora sp. K310 was isolated from Ghanaian mangrove river sediment. Spectroscopy-guided fractionation led to the isolation of two new compounds from the fermentation culture. One of the compounds is butremycin (2) which is the (3-hydroxyl) derivative of
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A new actinomycete strain Micromonospora sp. K310 was isolated from Ghanaian mangrove river sediment. Spectroscopy-guided fractionation led to the isolation of two new compounds from the fermentation culture. One of the compounds is butremycin (2) which is the (3-hydroxyl) derivative of the known Streptomyces metabolite ikarugamycin (1) and the other compound is a protonated aromatic tautomer of 5′-methylthioinosine (MTI) (3). Both new compounds were characterized by 1D, 2D NMR and MS data. Butremycin (2) displayed weak antibacterial activity against Gram-positive S. aureus ATCC 25923, the Gram-negative E. coli ATCC 25922 and a panel of clinical isolates of methicillin-resistant S. aureus (MRSA) strains while 3 did not show any antibacterial activity against these microbes. Full article
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Open AccessArticle Transcriptional Changes Caused by Bisphenol A in Oryzias javanicus, a Fish Species Highly Adaptable to Environmental Salinity
Mar. Drugs 2014, 12(2), 983-998; https://doi.org/10.3390/md12020983
Received: 10 December 2013 / Revised: 6 January 2014 / Accepted: 6 February 2014 / Published: 14 February 2014
Cited by 4 | PDF Full-text (725 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The Javanese medaka, Oryzias javanicus, is a fish highly adaptable to various environmental salinities. Here, we investigated the effects of the environmental pollutant bisphenol A (BPA; an endocrine disrupting chemical) on gene expression levels in this species acclimated to different salinities. Using
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The Javanese medaka, Oryzias javanicus, is a fish highly adaptable to various environmental salinities. Here, we investigated the effects of the environmental pollutant bisphenol A (BPA; an endocrine disrupting chemical) on gene expression levels in this species acclimated to different salinities. Using cDNA microarrays, we detected the induction of differential expression of genes by BPA, and compared the transcriptional changes caused by chemical exposure at different salinities. There were marked transcriptional changes induced by BPA between treatments. While 533 genes were induced by a factor of more than two when O. javanicus was exposed to BPA in seawater, only 215 genes were induced in freshwater. Among those genes, only 78 were shared and changed significantly their expression in both seawater and freshwater. Those genes were mainly involved in cellular processes and signaling pathway. We then categorized by functional group genes specifically induced by BPA exposure in seawater or freshwater. Gene expression changes were further confirmed in O. javanicus exposed to various concentrations of BPA, using quantitative real-time reverse transcription PCR based on primer sets for 28 selected genes. Full article
(This article belongs to the Special Issue Marine Fish Endocrine Disruption)
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Open AccessArticle Dietary Fucoxanthin Increases Metabolic Rate and Upregulated mRNA Expressions of the PGC-1alpha Network, Mitochondrial Biogenesis and Fusion Genes in White Adipose Tissues of Mice
Mar. Drugs 2014, 12(2), 964-982; https://doi.org/10.3390/md12020964
Received: 17 December 2013 / Revised: 22 January 2014 / Accepted: 23 January 2014 / Published: 14 February 2014
Cited by 10 | PDF Full-text (1460 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The mechanism for how fucoxanthin (FX) suppressed adipose accumulation is unclear. We aim to investigate the effects of FX on metabolic rate and expressions of genes related to thermogenesis, mitochondria biogenesis and homeostasis. Using a 2 × 2 factorial design, four groups of
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The mechanism for how fucoxanthin (FX) suppressed adipose accumulation is unclear. We aim to investigate the effects of FX on metabolic rate and expressions of genes related to thermogenesis, mitochondria biogenesis and homeostasis. Using a 2 × 2 factorial design, four groups of mice were respectively fed a high sucrose (50% sucrose) or a high-fat diet (23% butter + 7% soybean oil) supplemented with or without 0.2% FX. FX significantly increased oxygen consumption and carbon dioxide production and reduced white adipose tissue (WAT) mass. The mRNA expressions of peroxisome proliferator-activated receptor (PPAR) γ coactivator-1α (PGC-1α), cell death-inducing DFFA-like effecter a (CIDEA), PPARα, PPARγ, estrogen-related receptor α (ERRα), β3-adrenergic receptor (β3-AR) and deiodinase 2 (Dio2) were significantly upregulated in inguinal WAT (iWAT) and epididymal WAT (eWAT) by FX. Mitochondrial biogenic genes, nuclear respiratory factor 1 (NRF1) and NRF2, were increased in eWAT by FX. Noticeably, FX upregulated genes of mitochondrial fusion, mitofusin 1 (Mfn1), Mfn2 and optic atrophy 1 (OPA1), but not mitochondrial fission, Fission 1, in both iWAT and eWAT. In conclusion, dietary FX enhanced the metabolic rate and lowered adipose mass irrespective of the diet. These were associated with upregulated genes of the PGC-1α network and mitochondrial fusion in eWAT and iWAT. Full article
(This article belongs to the Special Issue Marine Carotenoids (Special Issue))
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Open AccessArticle Antimicrobial Activity of the Marine Alkaloids, Clathrodin and Oroidin, and Their Synthetic Analogues
Mar. Drugs 2014, 12(2), 940-963; https://doi.org/10.3390/md12020940
Received: 25 November 2013 / Revised: 17 January 2014 / Accepted: 23 January 2014 / Published: 14 February 2014
Cited by 23 | PDF Full-text (939 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Marine organisms produce secondary metabolites that may be valuable for the development of novel drug leads as such and can also provide structural scaffolds for the design and synthesis of novel bioactive compounds. The marine alkaloids, clathrodin and oroidin, which were originally isolated
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Marine organisms produce secondary metabolites that may be valuable for the development of novel drug leads as such and can also provide structural scaffolds for the design and synthesis of novel bioactive compounds. The marine alkaloids, clathrodin and oroidin, which were originally isolated from sponges of the genus, Agelas, were prepared and evaluated for their antimicrobial activity against three bacterial strains (Enterococcus faecalis, Staphylococcus aureus and Escherichia coli) and one fungal strain (Candida albicans), and oroidin was found to possess promising Gram-positive antibacterial activity. Using oroidin as a scaffold, 34 new analogues were designed, prepared and screened for their antimicrobial properties. Of these compounds, 12 exhibited >80% inhibition of the growth of at least one microorganism at a concentration of 50 µM. The most active derivative was found to be 4-phenyl-2-aminoimidazole 6h, which exhibited MIC90 (minimum inhibitory concentration) values of 12.5 µM against the Gram-positive bacteria and 50 µM against E. coli. The selectivity index between S. aureus and mammalian cells, which is important to consider in the evaluation of a compound’s potential as an antimicrobial lead, was found to be 2.9 for compound 6h. Full article
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Open AccessArticle Synthesis of PPAR-γ Activators Inspired by the Marine Natural Product, Paecilocin A
Mar. Drugs 2014, 12(2), 926-939; https://doi.org/10.3390/md12020926
Received: 24 December 2013 / Revised: 10 January 2014 / Accepted: 22 January 2014 / Published: 13 February 2014
Cited by 5 | PDF Full-text (927 KB) | HTML Full-text | XML Full-text
Abstract
A series of N-substituted phthalimide derivatives were synthesized based on a pharmacophore study of paecilocin A (a natural PPAR-γ agonist) and synthetic leads. The introduction of hydrophilic and hydrophobic groups to the phthalimide skeleton yielded compounds 314. Compound 7
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A series of N-substituted phthalimide derivatives were synthesized based on a pharmacophore study of paecilocin A (a natural PPAR-γ agonist) and synthetic leads. The introduction of hydrophilic and hydrophobic groups to the phthalimide skeleton yielded compounds 314. Compound 7 showed significant PPAR-γ activation in a luciferase assay using rat liver Ac2F cells. Docking simulations showed that a free hydroxyl group on the phthalimide head and a suitable hydrophilic tail, including a phenyl linker, were beneficial for PPAR-γ activation. Compound 7 and rosiglitazone concentration-dependently activated PPAR-γ with EC50 values of 0.67 μM and 0.028 μM, respectively. These phthalimide derivatives could be further investigated as a new class of PPAR-γ ligands. Full article
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