14,637 results match your criteria Bioorg. Med. Chem.[Journal]


Biomimetic synthetic studies on meroterpenoids from the marine sponge Aka coralliphaga: Divergent total syntheses of siphonodictyal B, liphagal and corallidictyals A-D.

Bioorg Med Chem 2019 Feb 19. Epub 2019 Feb 19.

Department of Chemistry, University of Adelaide, Adelaide, SA 5005, Australia. Electronic address:

The marine sponge Aka coralliphaga is a rich source of biologically active and structurally interesting meroterpenoids. Inspired by these natural products, we have used biosynthetic speculation to devise biomimetic syntheses of siphonodictyal B, liphagal and corallidictyals A-D from sclareolide. This work resulted in the development of new cascade reactions in the synthesis of liphagal, the reassignment of the structure of siphonodictyal B, and the realisation that corallidictyals A and B are possibly isolation artefacts. Read More

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http://dx.doi.org/10.1016/j.bmc.2019.02.038DOI Listing
February 2019

Synthesis, characterization, and photodynamic therapy activity of 5,10,15,20-Tetrakis(carboxyl)porphyrin.

Bioorg Med Chem 2019 Mar 27. Epub 2019 Mar 27.

Department of Biochemistry and Molecular Biology, Guangdong Medical University, Zhanjiang 524023, PR China. Electronic address:

Water-soluble porphyrins are considered promising drug candidates for photodynamic therapy (PDT). This study investigated the PDT activity of a new water-soluble, anionic porphyrin (1-Zn), which possesses four negative charges. The photodynamic anticancer activity of 1-Zn was investigated by the MTT assay, with mTHPC as a positive control. Read More

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http://dx.doi.org/10.1016/j.bmc.2019.03.051DOI Listing

Is it possible to track intracellular chitosan nanoparticles using magnetic nanoparticles as contrast agent?

Bioorg Med Chem 2019 Apr 6. Epub 2019 Apr 6.

Biotechnology, Institute of Tropical Pathology and Public Health, Universidade Federal de Goiás, Goiânia, GO 74605-050, Brazil. Electronic address:

Drug delivery systems prepared with nanostructures are able to overcome biological barriers. However, one of the main challenges in the use of these nanosystems is their internalization by macrophages. This study aims to prepare and characterize chitosan nanoparticles incorporating maghemite nanoparticles and investigate their intracellular tracking in RAW 264. Read More

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http://dx.doi.org/10.1016/j.bmc.2019.04.011DOI Listing

Benzofuran-isatin hybrids tethered via different length alkyl linkers and their in vitro anti-mycobacterial activities.

Bioorg Med Chem 2019 Apr 10. Epub 2019 Apr 10.

Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, PR China. Electronic address:

A series of novel benzofuran-isatin hybrids 6a-m tethered through different length alkyl linkers propylene, butylene, pentylene and hexylene were designed, synthesized and evaluated for their in vitro anti-mycobacterial activities against both drug-susceptible and multi-drug resistant (MDR) Mycobacterium tuberculosis (MTB) and cytotoxicity towards VERO cells. All hybrids with acceptable cytotoxicity in VERO cells (CC: 64 to >1024 μg/mL) also exhibited considerable anti-mycobacterial activities against both drug-susceptible and MDR-MTB strains with MIC in a range of 0.125-4 μg/mL. Read More

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http://dx.doi.org/10.1016/j.bmc.2019.04.017DOI Listing

Development of Tc-labeled trivalent isonitrile radiotracer for folate receptor imaging.

Bioorg Med Chem 2019 Apr 10. Epub 2019 Apr 10.

Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Republic of Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address:

Folate receptors (FR) are frequently overexpressed in a wide variety of human cancers. The aim of this study was to develop a trivalent Tc(CO)-labeled folate radiotracer containing isonitrile (CN-R) as the coordinating ligand for FR target imaging. [Tc]Tc-10 was HPLC purified (>98% chemical purity) and evaluated in vitro and in vivo as a potential agent for targeting FR-positive KB cells. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S09680896193005
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http://dx.doi.org/10.1016/j.bmc.2019.04.013DOI Listing
April 2019
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Novel 7-formyl-naphthyridyl-ureas derivatives as potential selective FGFR4 inhibitors: Design, synthesis, and biological activity studies.

Bioorg Med Chem 2019 Apr 10. Epub 2019 Apr 10.

Jiangsu Province Hi-Tech Key Laboratory for Bio-medical Research and School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China. Electronic address:

Total twenty-five 7-formyl-naphthyridyl-urea derivatives were designed, synthesized and evaluated for their inhibition of FGFR4 kinase and antitumor activity. The pharmacological data indicated that most of the tested compounds showed high selectivity towards FGFR4 kinase and could significantly inhibit FGFR4 and the tumor cells lines with the high expression of FGFR4. In particular, compounds 6f, 6g, 6h, 6l, 6m and 6s showed a good performance in pharmacokinetic tests. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S09680896193042
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http://dx.doi.org/10.1016/j.bmc.2019.04.018DOI Listing
April 2019
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New analogs of SYA013 as sigma-2 ligands with anticancer activity.

Bioorg Med Chem 2019 Apr 8. Epub 2019 Apr 8.

Division of Basic Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA.

Our previous study has revealed 4-(4-(4-chlorophenyl)-1,4-diazepan-1-yl)-1-(4-fluorophenyl)butan-1-one·2HCl (SYA013) 1 as a sigma ligand with moderate selectivity for the sigma-2 receptor. Given the overexpression of sigma receptors in solid tumors and reports of sigma ligands with anticancer activities, we selected 1 for evaluation in several solid tumor cell lines. In addition, we have synthesized new analogs of 1 and now report that several of them bind preferentially at the sigma-2 receptor and have shown inhibition of several cancer cell lines including MDA-MB-231, MDA-MB-486, A549, PC-3, MIA PaCa-2 and Panc-1 cells. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S09680896193039
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http://dx.doi.org/10.1016/j.bmc.2019.04.012DOI Listing
April 2019
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Evidence for ligandable sites in structured RNA throughout the Protein Data Bank.

Bioorg Med Chem 2019 Apr 6. Epub 2019 Apr 6.

Chemical Biology Laboratory, National Cancer Institute, Frederick, MD 21702, United States. Electronic address:

RNA has attracted considerable attention as a target for small molecules. However, methods to identify, study, and characterize suitable RNA targets have lagged behind strategies for protein targets. One approach that has received considerable attention for protein targets has been to utilize computational analysis to investigate ligandable "pockets" on proteins that are amenable to small molecule binding. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S09680896183214
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http://dx.doi.org/10.1016/j.bmc.2019.04.010DOI Listing
April 2019
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Synthesis and evaluation of bi-functional 7-hydroxycoumarin platinum(IV) complexes as antitumor agents.

Bioorg Med Chem 2019 Apr 6. Epub 2019 Apr 6.

Institute of Biopharmaceutical Research, Liaocheng University, Liaocheng 252059, China.

A series of bi-functional 7-hydroxycoumarin platinum(IV) complexes were synthesized, characterized, and evaluated for antitumor activities. The 7-hydroxycoumarin platinum(IV) complexes display moderate to effective antitumor activities toward the tested cell lines and show much potential in overcoming drug resistance of platinum(II) drugs. In reducing microenvironment, the title compounds could be reduced to platinum(II) complex accompanied with two equivalents of coumarin units. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S09680896183210
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http://dx.doi.org/10.1016/j.bmc.2019.04.009DOI Listing
April 2019
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Unveiling the druggable RNA targets and small molecule therapeutics.

Bioorg Med Chem 2019 Mar 30. Epub 2019 Mar 30.

Department of Biological Sciences, Auburn University, 120 W. Samford Ave, Rouse Life Sciences Building, Auburn, AL 36849, USA. Electronic address:

The increasing appreciation for the crucial roles of RNAs in infectious and non-infectious human diseases makes them attractive therapeutic targets. Coding and non-coding RNAs frequently fold into complex conformations which, if effectively targeted, offer opportunities to therapeutically modulate numerous cellular processes, including those linked to undruggable protein targets. Despite the considerable skepticism as to whether RNAs can be targeted with small molecule therapeutics, overwhelming evidence suggests the challenges we are currently facing are not outside the realm of possibility. Read More

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http://dx.doi.org/10.1016/j.bmc.2019.03.057DOI Listing

Chemical synthesis, microbial transformation and biological evaluation of tetrahydroprotoberberines as dopamine D1/D2 receptor ligands.

Bioorg Med Chem 2019 Apr 8. Epub 2019 Apr 8.

State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, China. Electronic address:

Dopamine D1/D2 receptors are important targets for drug discovery in the treatment of central nervous system diseases. To discover new and potential D1/D2 ligands, 17 derivatives of tetrahydroprotoberberine (THPB) with various substituents were prepared by chemical synthesis or microbial transformation using Streptomyces griseus ATCC 13273. Their functional activities on D1 and D2 receptors were determined by cAMP assay and calcium flux assay. Read More

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http://dx.doi.org/10.1016/j.bmc.2019.04.014DOI Listing
April 2019
2.793 Impact Factor

Scaffold hopping of fused piperidine-type NK3 receptor antagonists to reduce environmental impact.

Bioorg Med Chem 2019 Apr 1. Epub 2019 Apr 1.

Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan. Electronic address:

Neurokinin-3 receptor (NK3R) plays a pivotal role in the release of gonadotropin-releasing hormone in the hypothalamus-pituitary-gonadal (HPG) axis. To develop novel NK3R antagonists with less environmental toxicity, a series of heterocyclic scaffolds for the triazolopiperazine substructure in an NK3R antagonist fezolinetant were designed and synthesized. An isoxazolo[3,4-c]piperidine derivative exhibited moderate NK3R antagonistic activity and favorable properties that were decomposable under environmental conditions. Read More

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http://dx.doi.org/10.1016/j.bmc.2019.03.059DOI Listing

Chemical modifications of imidazole-containing alkoxyamines increase C-ON bond homolysis rate: Effects on their cytotoxic properties in glioblastoma cells.

Bioorg Med Chem 2019 Mar 18. Epub 2019 Mar 18.

Aix Marseille Univ, CNRS, ICR, Marseille, France; Aix Marseille Univ, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Marseille, France. Electronic address:

Previously, we described alkoxyamines bearing a pyridine ring as new pro-drugs with low molecular weights and theranostic activity. Upon chemical stimulus, alkoxyamines undergo homolysis and release free radicals, which can, reportedly, enhance magnetic resonance imaging and trigger cancer cell death. In the present study, we describe the synthesis and the anti-cancer activity of sixteen novel alkoxyamines that contain an imidazole ring. Read More

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http://dx.doi.org/10.1016/j.bmc.2019.03.029DOI Listing

Discovery, synthesis, biological evaluation and molecular docking study of (R)-5-methylmellein and its analogs as selective monoamine oxidase A inhibitors.

Bioorg Med Chem 2019 Apr 2. Epub 2019 Apr 2.

School of Pharmacy, Fudan University, No. 826 Zhangheng Road, Shanghai 201203, China. Electronic address:

(R)-5-Methylmellein (5-MM), the major ingredient in the fermented mycelia of the medicinal fungus Xylaria nigripes (called Wuling Shen in Chinese)¸ was found to be a selective inhibitor against monoamine oxidase A (MAO-A) and might play an important role in the clinical usage of this edible fungus as an anti-depressive traditional Chinese medicine (TCM). Based on the discovery and hypothesis, a variety of (R)-5-MM analogs were synthesized and evaluated in vitro against two monoamine oxidase isoforms (MAO-A and MAO-B). Most synthetic analogs showed selective inhibition of MAO-A with IC values ranging from 0. Read More

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http://dx.doi.org/10.1016/j.bmc.2019.03.060DOI Listing

6-Bromoindolglyoxylamido derivatives as antimicrobial agents and antibiotic enhancers.

Bioorg Med Chem 2019 Apr 4. Epub 2019 Apr 4.

School of Chemical Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand. Electronic address:

The combination of increased incidence of drug-resistant strains of bacteria and a lack of novel drugs in development creates an urgency for the search for new antimicrobials. Initial screening of compounds from an in-house library identified two 6-bromoindolglyoxylamide polyamine derivatives (3 and 4) that exhibited intrinsic antimicrobial activity towards Gram-positive bacteria, Staphylococcus aureus and S. intermedius with polyamine 3 also displaying in vitro antibiotic enhancing properties against the resistant Gram-negative bacterium Pseudomonas aeruginosa. Read More

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http://dx.doi.org/10.1016/j.bmc.2019.04.004DOI Listing
April 2019
2 Reads

Characterising covalent warhead reactivity.

Bioorg Med Chem 2019 Apr 3. Epub 2019 Apr 3.

Drug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, University of Dundee, Dundee DD1 5EH, UK. Electronic address:

Many drugs currently used are covalent inhibitors and irreversibly inhibit their targets. Most of these were discovered through serendipity. Covalent inhibitions can have many advantages from a pharmacokinetic perspective. Read More

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http://dx.doi.org/10.1016/j.bmc.2019.04.002DOI Listing
April 2019
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Syntheses and evaluation of a homologous series of aza-vesamicol as improved radioiodine-labeled probes for sigma-1 receptor imaging.

Bioorg Med Chem 2019 Mar 29. Epub 2019 Mar 29.

Graduate School of medical Sciences, Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan.

Sigma-1 receptor imaging probes for determining the expression levels are desirable for diagnoses of various diseases and companion diagnoses of therapeutic agents targeting the sigma-1 receptor. In this study, we aimed to develop probes with higher affinity for the sigma-1 receptor. For this purpose, we synthesized and evaluated compounds, namely, vesamicol derivatives, in which alkyl chains of varying chain length were introduced between a piperazine ring and a benzene ring. Read More

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http://dx.doi.org/10.1016/j.bmc.2019.03.054DOI Listing

Synthesis and characterization of hydrogen peroxide activated estrogen receptor beta ligands.

Bioorg Med Chem 2019 Apr 3. Epub 2019 Apr 3.

Department of Chemistry, University of Richmond, 138 UR Drive, Richmond, VA 23173, USA. Electronic address:

The development and evaluation of selective estrogen receptor modulators (SERMs) is of interest because of the complex and significant role of estrogen receptors in normal tissues as well as disease states. In neurodegenerative disorders such as Alzheimer's disease and multiple sclerosis, estrogen receptor beta (ERβ) seems to provide a protective anti-inflammatory response. Due to the increase in reactive oxygen species (ROS) in these diseases, we have masked ERβ ligands, including diarylpropionitrile (DPN), as boronate esters that release the active estrogen in the presence of HO. Read More

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http://dx.doi.org/10.1016/j.bmc.2019.04.003DOI Listing
April 2019
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Kinase inhibitions in pyrido[4,3-h] and [3,4-g]quinazolines: Synthesis, SAR and molecular modeling studies.

Bioorg Med Chem 2019 Apr 4. Epub 2019 Apr 4.

Université Clermont Auvergne, CNRS, SIGMA Clermont, ICCF, F-63000 Clermont-Ferrand, France. Electronic address:

New pyrido[3,4-g]quinazoline derivatives were prepared and evaluated for their inhibitory potency toward 5 protein kinases (CLK1, DYRK1A, GSK3, CDK5, CK1). A related pyrido[4,3-h]quinazoline scaffold with an angular structure was also synthesized and its potency against the same protein kinase panel was compared to the analogous pyrido[3,4-g]quinazoline. Best results were obtained for 10-nitropyrido[3,4-g]quinazoline 4 toward CLK1 with nanomolar activities. Read More

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http://dx.doi.org/10.1016/j.bmc.2019.04.005DOI Listing

Antitumor effect of chiral organotelluranes elicited in a murine melanoma model.

Bioorg Med Chem 2019 Mar 21. Epub 2019 Mar 21.

Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, Brazil. Electronic address:

Protease roles in cancer progression have been demonstrated and their inhibitors display antitumor effects. Cathepsins are lysosomal cysteine proteases that have increased expression in tumor cells, and tellurium compounds were described as potent cysteine protease inhibitors and also assayed in several animal models. In this work, the two enantiomeric forms of 1-[Butyl(dichloro)-λ-tellanyl]-2-[1S-methoxyethyl]benzene (organotelluranes RF-13R and RF-13S) were evaluated as inhibitors of cathepsins B and L, showing significant enantiodiscrimination. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S09680896193008
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http://dx.doi.org/10.1016/j.bmc.2019.03.032DOI Listing
March 2019
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Synthesis and structure-activity relationships for new 6-fluoroquinoline derivatives with antiplasmodial activity.

Bioorg Med Chem 2019 Apr 2. Epub 2019 Apr 2.

Institute of Pharmaceutical Sciences, Pharmaceutical Chemistry, University of Graz, Schubertstraße 1, A-8010 Graz, Austria. Electronic address:

The substitution of 6-fluoroquinolines was modified in ring positions 2 and 4. The new compounds were tested in vitro for their activities against a sensitive and a multidrug resistant strain of Plasmodium falciparum. Some physicochemical parametres were calculated (log P, log D, ligand efficiency) or determined experimentally (permeability). Read More

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http://dx.doi.org/10.1016/j.bmc.2019.03.061DOI Listing

Specific stabilization of DNA G-quadruplex structures with a chemically modified complementary probe.

Bioorg Med Chem 2019 Mar 29. Epub 2019 Mar 29.

Key Laboratory of Biomedical Polymers-Ministry of Education, College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, China; The Institute for Advanced Studies, Wuhan University, Wuhan 430072, China. Electronic address:

The DNA G-quadruplex is an important higher-order structure formed from guanine-rich DNA sequences. There are many molecules which can stabilize this structure. However, the selectivity of these ligands to different G-quadruplexes was not satisfactory. Read More

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http://dx.doi.org/10.1016/j.bmc.2019.03.053DOI Listing

Anticancer profile of newly synthesized BRAF inhibitors possess 5-(pyrimidin-4-yl)imidazo[2,1-b]thiazole scaffold.

Bioorg Med Chem 2019 Apr 2. Epub 2019 Apr 2.

Center for Biomaterials, Korea Institute of Science & Technology (KIST School), Seoul, Seongbuk-gu 02792, Republic of Korea; University of Science & Technology (UST), Daejeon, Yuseong-gu 34113, Republic of Korea; Department of Biomolecular Science, University of Science & Technology (UST), Daejeon, Yuseong-gu 34113, Republic of Korea. Electronic address:

In this work, a new series of imidazo[2,1-b]thiazole was designed and synthesized. The new compounds are having 3-fluorophenyl at position 6 of imidazo[2,1-b]thiazole and pyrimidine ring at position 5. The pyrimidine ring containing either amide or sulphonamide moiety attached to a linker (ethyl or propyl) at position 2 of the pyrimidine ring. Read More

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http://dx.doi.org/10.1016/j.bmc.2019.03.062DOI Listing

The unexplored potential of quinone methides in chemical biology.

Bioorg Med Chem 2019 Apr 2. Epub 2019 Apr 2.

Imperial College London, Department of Chemistry, Molecular Science Research Hub, Wood Lane, W12 0BZ London, UK. Electronic address:

Quinone methides (QMs) are transient reactive species that can be efficiently generated from stable precursors under a variety of biocompatible conditions. Due to their electrophilic nature, QMs have been widely explored as cross-linking agents of DNA and proteins under physiological conditions. However, QMs also have a diene character and can irreversibly react via Diels-Alder reaction with electron-rich dienophiles. Read More

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http://dx.doi.org/10.1016/j.bmc.2019.04.001DOI Listing

Proline-based hydroxamates targeting the zinc-dependent deacetylase LpxC: Synthesis, antibacterial properties, and docking studies.

Bioorg Med Chem 2019 Mar 30. Epub 2019 Mar 30.

Institute of Organic Chemistry, University of Hamburg, Martin-Luther-King-Platz 6, 20146 Hamburg, Germany; German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Germany. Electronic address:

The Zn-dependent deacetylase LpxC is an essential enzyme in Gram-negative bacteria, which has been validated as antibacterial drug target. Herein we report the chiral-pool synthesis of novel d- and l-proline-derived 3,4-dihydroxypyrrolidine hydroxamates and compare their antibacterial and LpxC inhibitory activities with the ones of 4-monosubstituted and 3,4-unsubstituted proline derivatives. With potent antibacterial activities against several Gram-negative pathogens, the l-proline-based tertiary amine 41g ((S)-N-hydroxy-1-(4-{[4-(morpholinomethyl)phenyl]ethynyl}benzyl)pyrrolidine-2-carboxamide) was found to be the most active antibacterial compound within the investigated series, also showing some selectivity toward EcLpxC (K = 1. Read More

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http://dx.doi.org/10.1016/j.bmc.2019.03.056DOI Listing

Synthesis of isochroman-4-ones and 2H-pyran-3(6H)-ones by gold-catalyzed oxidative cycloalkoxylation of alkynes.

Bioorg Med Chem 2019 Mar 30. Epub 2019 Mar 30.

Department of Chemistry and Biomolecular Sciences, University of Ottawa, K1N 6N5 Ottawa, Canada. Electronic address:

Gold catalysis is a convenient tool to oxidatively functionalize alkyne into a range of valuable compounds. In this article, we report a new access to isochroman-4-one and 2H-pyran-3(6H)-one derivatives that involves a gold-catalyzed oxidative cycloalkoxylation of an alkyne in the presence of a pyridine N-oxide. The reaction proceeds under mild conditions, is relatively efficient and exhibits a high functional group compatibility. Read More

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http://dx.doi.org/10.1016/j.bmc.2019.03.055DOI Listing
March 2019
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Inhibition of pre-miRNA-136 processing by Dicer with small molecule BzDANP suggested the formation of ternary complex of pre-miR-136-BzDANP-Dicer.

Bioorg Med Chem 2019 Mar 18. Epub 2019 Mar 18.

Department of Regulatory Bioorganic Chemistry, The Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki, Osaka 567-0047, Japan. Electronic address:

Small-molecule modulators, along with antisense oligonucleotide, would be powerful tools and potential drug candidates for modulating miRNA-related gene expressions. The mechanism of the inhibitory effect of the C-bulge binding small molecule BzDANP for the Dicer processing reaction of pre-miR-136 was discussed on the data obtained by SPR, NMR, and kinetic analysis for Dicer processing. SPR and NMR analysis showed the preference of BzDANP binding to the C-bulge. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S09680896183217
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http://dx.doi.org/10.1016/j.bmc.2019.03.031DOI Listing
March 2019
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Dispiropyrrolidinyl-piperidone embedded indeno[1,2-b]quinoxaline heterocyclic hybrids: Synthesis, cholinesterase inhibitory activity and their molecular docking simulation.

Bioorg Med Chem 2019 Mar 30. Epub 2019 Mar 30.

Department of Biosciences, Sri Sathya Sai Institute of Higher Learning, Prasanthi Nilayam, A.P. 515 134, India.

A small library of new class of dispiropyrrolidinyl-piperidone tethered indono[1,2-b]quinoxaline heterocyclic hybrids 7a-j were synthesized employing multicomponent 1,3-dipolar cycloaddition strategy in [bmim]Br. The azomethine ylide employed is first of its kind and generated in situ from indenoquinoxalinone and l-tryptophan, a combination that has not been employed previously for the in situ generation of azomethine ylides. The synthesized heterocyclic hybrids 7a-j were evaluated for their in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities, therein compounds 7h and 7j displayed more potent AChE and BChE enzyme inhibition than the standard drug with IC values of 3. Read More

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http://dx.doi.org/10.1016/j.bmc.2019.03.058DOI Listing

Identification and design of novel small molecule inhibitors against MERS-CoV papain-like protease via high-throughput screening and molecular modeling.

Bioorg Med Chem 2019 Mar 26. Epub 2019 Mar 26.

Center for Biomolecular Sciences and Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 900 S. Ashland, IL 60607, USA. Electronic address:

The development of new therapeutic agents against the coronavirus causing Middle East Respiratory Syndrome (MERS) is a continuing imperative. The initial MERS-CoV epidemic was contained entirely through public health measures, but episodic cases continue, as there are currently no therapeutic agents effective in the treatment of MERS-CoV, although multiple strategies have been proposed. In this study, we screened 30,000 compounds from three different compound libraries against one of the essential proteases, the papain-like protease (PL), using a fluorescence-based enzymatic assay followed by surface plasmon resonance (SPR) direct binding analysis for hit confirmation. Read More

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http://dx.doi.org/10.1016/j.bmc.2019.03.050DOI Listing

Structure-activity relationship study of estrogen receptor down-regulators with a diphenylmethane skeleton.

Bioorg Med Chem 2019 Mar 26. Epub 2019 Mar 26.

Institute for Quantitative Biosciences, the University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan. Electronic address:

Selective estrogen receptor (ER) down-regulators (SERDs) are pure ER antagonists that also induce ER degradation upon binding to the receptor. Although SERDs have been developed for the treatment of ER-positive breast cancers for nearly a decade, their precise mechanism(s) of action and structure-activity relationship are still unclear. Generally, Western blotting is used to examine the effects of SERDs on ER protein levels, but the methodology is low-throughput and not quantitative. Read More

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http://dx.doi.org/10.1016/j.bmc.2019.03.042DOI Listing

Discovery of thiazolidin-4-one urea analogues as novel multikinase inhibitors that potently inhibit FLT3 and VEGFR2.

Bioorg Med Chem 2019 Mar 25. Epub 2019 Mar 25.

Department of Bioengineering, Zhuhai Campus of Zunyi Medical University, Zhuhai 519041, Guangdong Province, China. Electronic address:

A series of novel thiazolidine-4-one urea analogues were designed, synthesized and biologically evaluated. The structure-activity relationship (SAR) at several positions of the scaffolds was investigated and its binding mode was analyzed by molecular modeling studies. Compound 17b proved to be the most potent one, and IC values against A549 and HT-29 cancer cell lines were 0. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S09680896193034
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http://dx.doi.org/10.1016/j.bmc.2019.03.049DOI Listing
March 2019
1 Read

Purification, structural elucidation, antioxidant capacity and neuroprotective potential of the main polyphenolic compounds contained in Achyrocline satureioides (Lam) D.C. (Compositae).

Bioorg Med Chem 2019 Mar 25. Epub 2019 Mar 25.

Plataforma de Servicios Analíticos, Instituto de Investigaciones Biológicas Clemente Estable, 11600 Montevideo, Uruguay; Departamento de Neuroquímica, Instituto de Investigaciones Biológicas Clemente Estable, 11600 Montevideo, Uruguay. Electronic address:

Achyrocline satureioides (Lam) D.C (Compositae) is a native medicinal plant of South America traditionally utilized for its anti-inflammatory, sedative and anti-atherosclerotic properties among others. Neuroprotective effects have been reported in vivo and could be associated to its elevated content of flavonoid aglycones. Read More

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http://dx.doi.org/10.1016/j.bmc.2019.03.047DOI Listing
March 2019
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Establishing cell painting in a smaller chemical biology lab - A report from the frontier.

Bioorg Med Chem 2019 Mar 27. Epub 2019 Mar 27.

Department of Chemistry - Aarhus University, Langelandsgade 140, DK-8000, Denmark. Electronic address:

In this paper we will outline the efforts we have made recently to establish the profiling platform known as cell painting in our laboratory. This platform, which is based on fluorescence microscopy, allows rapid and cheap access to bioactivity fingerprints for small molecules and thereby can contribute with important information in many experimental situations that is faced in laboratories involved in molecular probe design, mode-of-action studies or that perform focused phenotypic screens. We have tried to achieve the following two objectives: (1) provide a detailed description of the hurdles that we had to overcome during establishment and describe our final protocol; (2) provide a more pedagogical description of the different methods used to analyse and represent data from this experiment. Read More

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http://dx.doi.org/10.1016/j.bmc.2019.03.052DOI Listing
March 2019
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Development of a platform for activatable fluorescent substrates of glucose transporters (GLUTs).

Bioorg Med Chem 2019 Mar 1. Epub 2019 Mar 1.

Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan; Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan; CREST, Japan Agency for Medical Research and Development (AMED), Chiyoda-ku, Tokyo 100-0004, Japan. Electronic address:

We have developed a platform for activatable fluorescent substrates of glucose transporters (GLUTs). We firstly conjugated fluorescein to glucosamine via an amide or methylene linker at the C-2 position of d-glucosamine, but the resulting compounds, FLG1 and FLG2, showed no uptake into MIN6 cells. So, we changed the fluorophore moiety to a fluorescein analogue, 2-Me TokyoGreen, which is less negatively charged. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S09680896183217
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http://dx.doi.org/10.1016/j.bmc.2019.02.055DOI Listing
March 2019
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Profiling withanolide A for therapeutic targets in neurodegenerative diseases.

Bioorg Med Chem 2019 Mar 13. Epub 2019 Mar 13.

Department of Chemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland. Electronic address:

To identify new potential therapeutic targets for neurodegenerative diseases, we initiated activity-based protein profiling studies with withanolide A (WitA), a known neuritogenic constituent of Withania somnifera root with unknown mechanism of action. Molecular probes were designed and synthesized, and led to the discovery of the glucocorticoid receptor (GR) as potential target. Molecular modeling calculations using the VirtualToxLab predicted a weak binding affinity of WitA for GR. Read More

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http://dx.doi.org/10.1016/j.bmc.2019.03.022DOI Listing
March 2019
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In silico study of M18 aspartyl amino peptidase (M18AAP) of Plasmodium vivax as an antimalarial drug target.

Bioorg Med Chem 2019 Mar 22. Epub 2019 Mar 22.

School of Biotechnology, KIIT University, Bhubaneswar 751024, Odisha, India. Electronic address:

Plasmodium vivax (Pv) is the second most malaria causing pathogen among Plasmodium species. M18 aspartic aminopeptidase (M18AAP) protein is a single gene copy present in Plasmodium. This protein is functional at the terminal stage of hemoglobin degradation of host and completes the hydrolysis process which makes it an important target for new chemotherapeutics. Read More

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http://dx.doi.org/10.1016/j.bmc.2019.03.039DOI Listing
March 2019
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Structure and biological evaluation of new cyclic and acyclic laxaphycin-A type peptides.

Bioorg Med Chem 2019 Mar 26. Epub 2019 Mar 26.

PSL Research University, EPHE-UPVD-CNRS, USR 3278 CRIOBE, Université de Perpignan, 52 Avenue Paul Alduy, 66860 Perpignan Cedex, France; Laboratoire d'Excellence "CORAIL", France. Electronic address:

Five new laxaphycins were isolated and fully characterised from the bloom forming cyanobacteria Anabaena torulosa sampled from Moorea, French Polynesia: three acyclic laxaphycin A-type peptides, acyclolaxaphycin A (1), [des-Gly]acyclolaxaphycin A (2) and [des-(Leu-Gly)]acyclolaxaphycin A (3), as well as two cyclic ones, [l-Val]laxaphycin A (4) and [d-Val]laxaphycin A (5). The absolute configuration of the amino acids, established using advanced Marfey's analysis for compounds 2-5, highlights a conserved stereochemistry at the Cα carbons of the peptide ring that is characteristic of this family. To the best of our knowledge, this is the first report of acyclic analogues within the laxaphycin A-type peptides. Read More

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http://dx.doi.org/10.1016/j.bmc.2019.03.046DOI Listing
March 2019
2 Reads

Discovery of potent anti-inflammatory 4-(4,5,6,7-tetrahydrofuro[3,2-c]pyridin-2-yl) pyrimidin-2-amines for use as Janus kinase inhibitors.

Bioorg Med Chem 2019 Mar 25. Epub 2019 Mar 25.

Jiangsu Simcere Pharmaceutical Co. Ltd., Jiangsu Key Laboratory of Molecular Targeted Antitumor Drug Research, No 699-18, Xuanwu District, Nanjing 210042, PR China; Nanjing Noratech Pharmaceutical Co. Ltd., No 9 Weidi Road, Jiangsu Life Park, Qixia District, Nanjing 210046, PR China. Electronic address:

The Janus kinase (JAK) family of tyrosine kinases has been proven to provide targeted immune modulation. Orally available JAK inhibitors have been used for the treatment of immune-mediated inflammatory diseases, such as rheumatoid arthritis (RA). Here, we report the design, synthesis and biological evaluation of 4-(4,5,6,7-tetrahydrofuro[3,2-c]pyridin-2-yl) pyrimidin-2-amino derivatives as JAK inhibitors. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S09680896193037
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http://dx.doi.org/10.1016/j.bmc.2019.03.048DOI Listing
March 2019
7 Reads
2.793 Impact Factor

Syntheses and bioactivities of songorine derivatives as novel G protein-coupled receptor antagonists.

Bioorg Med Chem 2019 May 23;27(9):1903-1910. Epub 2019 Mar 23.

College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, China; Shanghai Engineering Research Center of Aquatic-Product Processing & Preservation, Shanghai 201306, China; Laboratory of Quality and Safety Risk Assessment for Aquatic Products on Storage and Preservation (Shanghai), Ministry of Agriculture, Shanghai 201306, China. Electronic address:

Songorine isolated from Aconitum brachypodum Diels possesses prominent activity of inhibiting G protein-coupled receptors (GPCRs) in the early screening process. In this paper, a series of Songorine derivatives were synthesized and their inhibitory activities on GPCRs were also evaluated by using the Double Antibody Sandwich ELISA (DAS-ELISA) in vitro. Among them, three derivatives (3a, 4, 7) exhibited significant inhibitory activity against GPCRs with IC values of 0. Read More

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http://dx.doi.org/10.1016/j.bmc.2019.03.045DOI Listing
May 2019
2.793 Impact Factor

Effect of curcumin-nanoemulsion associated with photodynamic therapy in breast adenocarcinoma cell line.

Bioorg Med Chem 2019 May 22;27(9):1882-1890. Epub 2019 Mar 22.

UNESP - São Paulo State University - IBILCE - Institute of Biosciences, Humanities and Exact Sciences - Department of Biology - Rua Cristóvão Colombo, 2265 - Bairro Jardim Nazareth, CEP 15054-010 São José do Rio Preto, São Paulo, Brazil. Electronic address:

Curcumin, a natural compound has several antineoplastic activities and is a promising natural photosensitizer used in photodynamic therapy. However, its low solubility in physiological medium limit the clinical use of curcumin. This study aimed to analyze the action of curcumin-nanoemulsion, a new and well-designed Drug Delivery System (DDS+) molecule, used as a photosensitizing agent in photodynamic therapy in an in vitro breast cancer model, MCF-7 cells. Read More

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http://dx.doi.org/10.1016/j.bmc.2019.03.044DOI Listing

Binding pocket-based design, synthesis and biological evaluation of novel selective BRD4-BD1 inhibitors.

Bioorg Med Chem 2019 May 22;27(9):1871-1881. Epub 2019 Mar 22.

Department of Medicinal Chemistry, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, Hunan, PR China. Electronic address:

Bromodomain-containing protein 4 (BRD4), consisting of two tandem bromodomains (BD1 and BD2), is key epigenetic regulator in fibrosis and cancer, which has been reported that BD1 and BD2 have distinct roles in post-translational modification. But there are few selective inhibitors toward those two domains. Herein, this study designed and synthesized a series of novel selective BRD4-BD1 inhibitors, using computer-aided drug design (CADD) approach focused on exploring the difference of the binding pockets of BD1 and BD2, and finding the His437 a crucial way to achieve BRD4-BD1 selectivity. Read More

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http://dx.doi.org/10.1016/j.bmc.2019.03.037DOI Listing

Identification of highly potent and selective MMP2 inhibitors addressing the S1' subsite with d-proline-based compounds.

Bioorg Med Chem 2019 May 22;27(9):1891-1902. Epub 2019 Mar 22.

Department of Chemistry "Ugo Schiff", University of Florence, Via della Lastruccia 13, 50019 Sesto Fiorentino, Florence, Italy; Interdepartmental Center for Preclinical Development of Molecular Imaging (CISPIM), University of Florence, Viale Morgagni 85, 50134 Florence, Italy. Electronic address:

MMP2 and MMP9, also called gelatinases, play a primary role in the angiogenic switch, as a fundamental step of tumor progression, and show high degree of structural similarity. Clinically successful gelatinase inhibitors need to be highly selective as opposite effects have been found for the two enzymes, and the S1' subsite is the major driver to attain selective and potent inhibitors. The synthesis of d-proline-derived hydroxamic acids containing diverse appendages at the amino group, varying in length and decoration allowed to give insight on the MMP2/MMP9 selectivity around the S1' subsite, resulting in the identification of sub-nanomolar compounds with high selectivity up to 730. Read More

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http://dx.doi.org/10.1016/j.bmc.2019.03.043DOI Listing

Second-generation aryl isonitrile compounds targeting multidrug-resistant Staphylococcus aureus.

Bioorg Med Chem 2019 May 19;27(9):1845-1854. Epub 2019 Mar 19.

Department of Chemistry, Center for Cancer Research and Institute for Drug Discovery, Purdue University, 720 Clinic Drive, West Lafayette, IN 47907, United States; Purdue Institute of Inflammation, Immunology and Infectious Disease, 610 Purdue Mall, West Lafayette, IN 47907, United States. Electronic address:

Antibiotic resistance remains a major global public health threat that requires sustained discovery of novel antibacterial agents with unexploited scaffolds. Structure-activity relationship of the first-generation aryl isonitrile compounds we synthesized led to an initial lead molecule that informed the synthesis of a second-generation of aryl isonitriles. From this new series of 20 compounds, three analogues inhibited growth of methicillin-resistant Staphylococcus aureus (MRSA) (from 1 to 4 µM) and were safe to human keratinocytes. Read More

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http://dx.doi.org/10.1016/j.bmc.2019.03.034DOI Listing
May 2019
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New heteroaryl carbamates: Synthesis and biological screening in vitro and in mammalian cells of wild-type and mutant HIV-protease inhibitors.

Bioorg Med Chem 2019 May 21;27(9):1863-1870. Epub 2019 Mar 21.

Dipartimento di Scienze, Università della Basilicata, Via Ateneo Lucano 10, 85100 Potenza, Italy. Electronic address:

New heteroaryl HIV-protease inhibitors bearing a carbamoyl spacer were synthesized in few steps and high yield, from commercially available homochiral epoxides. Different substitution patterns were introduced onto a given isopropanoyl-sulfonamide core that can have either H or benzyl group. The in vitro inhibition activity against recombinant protease showed a general beneficial effect of both carbamoyl moiety and the benzyl group, ranging the IC values between 11 and 0. Read More

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http://dx.doi.org/10.1016/j.bmc.2019.03.041DOI Listing

Development of a dual-wavelength fluorescent nanoprobe for in vivo and in vitro cell tracking consecutively.

Bioorg Med Chem 2019 May 19;27(9):1855-1862. Epub 2019 Mar 19.

Bioengineering Department, University of Texas at Arlington, Arlington, TX, USA. Electronic address:

Many imaging probes have been developed for a wide variety of imaging modalities. However, no optical imaging probe could be utilized for both microscopic and whole animal imaging. To fill the gap, the dual-wavelength fluorescent imaging nanoprobe was developed to simultaneously carry both visible-range fluorescent dye and near-infrared (NIR) dye. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S09680896193016
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http://dx.doi.org/10.1016/j.bmc.2019.03.036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6469702PMC
May 2019
4 Reads

Design, synthesis, fungicidal activity and molecular docking studies of novel 2-((2-hydroxyphenyl)methylamino)acetamide derivatives.

Bioorg Med Chem 2019 Mar 20. Epub 2019 Mar 20.

Key Laboratory of Theoretical Organic Chemistry and Functional Molecular, Ministry of Education, Hunan University of Science and Technology, Xiangtan 411201, People's Republic of China.

A series of novel 2-hydroxyphenyl substituted aminoacetamides was designed by molecular hybridization of the aminoacetamide scaffold and 2-hydroxyphenyl motif. The target compounds were synthesized and their fungicidal activities were evaluated. Some of the target compounds showed excellent antifungal activities against S. Read More

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http://dx.doi.org/10.1016/j.bmc.2019.03.040DOI Listing

Polymorphs, co-crystal structure and pharmacodynamics study of MBRI-001, a deuterium-substituted plinabulin derivative as a tubulin polymerization inhibitor.

Bioorg Med Chem 2019 May 20;27(9):1836-1844. Epub 2019 Mar 20.

School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China; Innovation Center for Marine Drug Screening and Evaluation, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266071, China; Marine Biomedical Research Institute of Qingdao, Qingdao 266071, China. Electronic address:

MBRI-001, a deuterium-substituted plinabulin derivative, has been reported to have better pharmacokinetic and similar antitumor effects in comparison with plinabulin. In this approach, we further carried out its polymorphs, co-crystal structure of MBRI-001-tubulin and tubulin inhibition study. Among the different polymorphs, Form F (MBRI-001/HO) was prepared and evaluated, which had better physical stability and suitable process for scale-up production. Read More

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http://dx.doi.org/10.1016/j.bmc.2019.03.035DOI Listing

Neurodegeneration meets immunology - A chemical biology perspective.

Bioorg Med Chem 2019 May 20;27(9):1911-1924. Epub 2019 Mar 20.

University of Groningen, Department of Biomedical Sciences of Cells and Systems, University Medical Centre, Groningen, The Netherlands; Department Anatomy and Neuroscience, Free University Medical Center (VUmc), Amsterdam, The Netherlands. Electronic address:

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http://dx.doi.org/10.1016/j.bmc.2019.03.038DOI Listing

Betulinic acid induces apoptosis and inhibits metastasis of human colorectal cancer cells in vitro and in vivo.

Bioorg Med Chem 2019 Mar 19. Epub 2019 Mar 19.

Institute of Translational Pharmacology and Clinical Application of Sichuan Academy of Chinese Medicine Sciences, Sichuan Center for Translational Medicine of Traditional Chinese Medicine, Sichuan Engineering Technology Research Center of Genuine Regional Drug, Biological Assay Key Laboratory of State Administration of Traditional Chinese Medicine for TCM Quality, Sichuan Provincial Key Laboratory of Quality Evaluation and New Drug Creation of Traditional Chinese Medicine, Chengdu, Sichuan 610041, China. Electronic address:

Betulinic acid (BA) is a pentacyclic triterpenoids extracted from birch with a wide range of biological properties. Recent studies have shown that BA has significant cytotoxicity to various types of human cancer cells, and shows potential in cancer treatment. However, the efficacy of BA on human colorectal cancer tumor cells is still unclear. Read More

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http://dx.doi.org/10.1016/j.bmc.2019.03.033DOI Listing
March 2019
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Discovery of a novel class of potent and selective tetrahydroindazole-based sigma-1 receptor ligands.

Bioorg Med Chem 2019 May 16;27(9):1824-1835. Epub 2019 Mar 16.

Center for Molecular Innovation and Drug Discovery, Northwestern University, Evanston, IL 60208, United States; Department of Pharmacology, Northwestern University, Chicago, IL 60611, United States; Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States. Electronic address:

The sigma-1 and sigma-2 receptors have been shown to play important roles in CNS diseases, cancer, and other disorders. These findings suggest that targeting these proteins with small-molecule modulators may be of important therapeutic value. Here we report the development of a new class of tetrahydroindazoles that are highly potent and selective ligands for sigma-1. Read More

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http://dx.doi.org/10.1016/j.bmc.2019.03.030DOI Listing