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1. Allosteric small molecule modulators of nuclear receptors

Author:
Meijer, Femke A.; Leijten-van de Gevel, Iris A.; de Vries, Rens M.J.M.; Brunsveld, Luc
Source:
Molecular and cellular endocrinology 2019
ISSN:
0303-7207
Subject:
mechanism of action,   etc   ; drugs; ligands; receptors;     Show all 4 Subjects
Abstract:
... Nuclear Receptors (NRs) are multi-domain proteins, whose natural regulation occurs via ligands for a classical, orthosteric, binding pocket and via intra- and inter-domain allosteric mechanisms. Allosteric modulation of NRs via synthetic small molecules has recently emerged as an interesting entry to address the need for small molecules targeting NRs in pathology, via novel modes of action and wit ...
DOI:
10.1016/j.mce.2019.01.022

2. Exploring the mode of action of inhibitors targeting the PhoP response regulator of Salmonella enterica through comprehensive pharmacophore approaches

Author:
Tsai, Keng-Chang; Hung, Po-Pin; Cheng, Ching-Feng; Chen, Chinpan; Tseng, Tien-Sheng
Source:
RSC advances 2019 v.9 no.16 pp. 9308-9312
ISSN:
2046-2069
Subject:
mechanism of action,   etc   ; DNA; Salmonella enterica; models; pharmacology; virulence;     Show all 6 Subjects
Abstract:
... The PhoQ/PhoP two-component system regulates the physiological and virulence functions of Salmonella enterica. However, the mode of action of known PhoP inhibitors is unclear. We systematically constructed a pharmacophore model of inhibitors to probe the interface pharmacophore model of the PhoP dimer, coupling it with Ligplot analysis. We found that these inhibitors bind on the α5-helix, altering ...
DOI:
10.1039/c9ra00620f

3. Consumption rituals relating to food and drink: A review and research agenda

Author:
Ratcliffe, Eleanor; Baxter, Weston Lyle; Martin, Nathalie
Source:
Appetite 2019 v.134 pp. 86-93
ISSN:
0195-6663
Subject:
mechanism of action,   etc   ; cognition; consumer attitudes; models; social cohesion;     Show all 5 Subjects
Abstract:
... Rituals are common in relation to consumption of food and drink, and are related to psychosocial benefits such as social bonding, affective change, and enhanced consumer perceptions. However, theoretical understanding of food and drink consumption rituals, and empirical examination of their effects and mechanisms of action, is limited. In this literature review we show a need for greater theoretic ...
DOI:
10.1016/j.appet.2018.12.021

4. Correction to: Effect of mint oil against Botrytis cinerea on table grapes and its possible mechanism of action

Author:
Xueyan, Ren; Dandan, Song; Zhuo, Liang; Qingjun, Kong
Source:
European journal of plant pathology 2019 v.153 no.3 pp. 983
ISSN:
0929-1873
Subject:
mechanism of action,   etc   ; Botrytis cinerea; mint; oils; table grapes;     Show all 5 Subjects
Abstract:
... The author name “Ren Xueuan” should be corrected and read as “Ren Xueyan”. ...
DOI:
10.1007/s10658-018-01604-y

5. Grob-Type Fragmentation Releases Paracyclophane Ring Strain in a Late-Stage Precursor of Haouamine A

Author:
Cao, Liming; Wang, Chenbo; Wipf, Peter
Source:
Organic letters 2019 v.21 no.5 pp. 1538-1541
ISSN:
1523-7052
Subject:
mechanism of action,   etc   ; Suzuki reaction; chemical structure; chemoselectivity; lactams; pyridines;     Show all 6 Subjects
Abstract:
... A ketene [2 + 2]-addition, an intramolecular aldol reaction, a Suzuki–Miyaura coupling, and a chemoselective lactam reduction were used to prepare a late-stage precursor of haouamine A. Exposure to acid led to a Grob-type fragmentation of the strained 3-aza[7]paracyclophane ring, followed by a tandem Pictet–Spengler reaction of the intermediate iminium ion and conversion to a novel 1,4a-propanocyc ...
DOI:
10.1021/acs.orglett.9b00424

6. New half-sandwich ruthenium(ii) complexes as proteosynthesis inhibitors in cancer cells

Author:
BallesterThese authors contributed equally to this work., Francisco J.; Ortega, Enrique; Porto, Vanesa; Kostrhunova, Hana; Davila-Ferreira, Nerea; Bautista, Delia; Brabec, Viktor; Domínguez, Fernando; Santana, M. Dolores; Ruiz, José
Source:
Chemical communications 2019 v.55 no.8 pp. 1140-1143
ISSN:
1364-548X
Subject:
mechanism of action,   etc   ; chemical reactions; cytotoxicity; neoplasm cells; neoplasms; ruthenium;     Show all 6 Subjects
Abstract:
... Half-sandwich ruthenium(ii) complexes [(η⁶-p-cymene)Ru(C^N)-(X)]⁰/⁺ (X = Cl, py or 4-NMe₂-py) containing a cyclometalated 2-ppy or 1-ppz with a non-coordinated CHO group as a handle for further functionalization have been synthesized to achieve selective cytotoxicity to cancer cells, the more potent compounds acting as proteosynthesis inhibitors; this is a new mode of action for half-sandwich meta ...
DOI:
10.1039/c8cc09211g

7. Novel technologies to improve food safety and quality

Author:
Morales-de la Peña, M; Welti-Chanes, J; Martín-Belloso, O
Source:
Current opinion in food science 2019 v.30 pp. 1-7
ISSN:
2214-7993
Subject:
mechanism of action,   etc   ; cold; electric field; food safety; foods; technology; ultraviolet radiation;     Show all 7 Subjects
Abstract:
... The demand for fresh, healthy, convenient and safe foods has prompted the development of nonthermal technologies in the food area. Numerous investigations in high-hydrostatic pressures, pulsed electric fields, ultrasound, ultraviolet light, pulsed light and cold plasma have demonstrated their effectiveness to obtain safe products with high-quality standards compared to conventional processes. The ...
DOI:
10.1016/j.cofs.2018.10.009

8. N-hydroxypipecolic acid and salicylic acid: a metabolic duo for systemic acquired resistance

Author:
Hartmann, Michael; Zeier, Jürgen
Source:
Current opinion in plant biology 2019 v.50 pp. 44-57
ISSN:
1369-5266
Subject:
mechanism of action,   etc   ; Arabidopsis; biosynthesis; gene expression; immunity; lysine; regulatory sequences; salicylic acid; systemic acquired resistance;     Show all 9 Subjects
Abstract:
... Recent research has established that the pipecolate pathway, a three-step biochemical sequence from l-lysine to N-hydroxypipecolic acid (NHP), is central for plant systemic acquired resistance (SAR). NHP orchestrates SAR establishment in concert with the immune signal salicylic acid (SA). Here, we outline the biochemistry of NHP formation from l-Lys and address novel progress on SA biosynthesis in ...
DOI:
10.1016/j.pbi.2019.02.006

9. Deciphering the mode of action of pollutants impairing the fish larvae escape response with the vibrational startle response assay

Author:
Faria, Melissa; Bedrossiantz, Juliette; Prats, Eva; Rovira Garcia, Xavier; Gómez-Canela, Cristian; Piña, Benjamin; Raldúa, Demetrio
Source:
The Science of the total environment 2019 v.672 pp. 121-128
ISSN:
0048-9697
Subject:
mechanism of action,   etc   ; antagonists; escape behavior; fish larvae; habituation; imidacloprid; muscarine receptors; neurotoxicity; neurotransmitters; pollutants; scopolamine;     Show all 11 Subjects
Abstract:
... The escape response evoked by vibrational stimuli and its habituation, essential behaviors for fish larvae survival, can be altered by neurotoxic environmental pollutants commonly found in our aquatic ecosystems.In this study we have analyzed the suitability of the Vibrational Startle Response Assay (VSRA) to obtain mechanistic information about the mode of action (MoA) of the chemicals impairing ...
DOI:
10.1016/j.scitotenv.2019.03.469

10. Computational Modeling of Designed Ankyrin Repeat Protein Complexes with Their Targets

Author:
Radom, Filip; Paci, Emanuele; Plückthun, Andreas
Source:
Journal of molecular biology 2019
ISSN:
0022-2836
Subject:
mechanism of action,   etc   ; X-ray diffraction; antibodies; biopharmaceuticals; diagnostic techniques; engineering; evolution; models; proteins;     Show all 9 Subjects
Abstract:
... Recombinant therapeutic proteins are playing an ever-increasing role in the clinic. High-affinity binding candidates can be produced in a high-throughput manner through the process of selection and evolution from large libraries, but the structures of the complexes with target protein can only be determined for a small number of them in a costly, low-throughput manner, typically by x-ray crystallo ...
DOI:
10.1016/j.jmb.2019.05.005

11. Creation of a Curated Aquatic Toxicology Database: EnviroTox

Author:
Connors, Kristin A.; Beasley, Amy; Barron, Mace G.; Belanger, Scott E.; Bonnell, Mark; Brill, Jessica L.; de Zwart, Dick; Kienzler, Aude; Krailler, Jesse; Otter, Ryan; Phillips, Joshua L.; Embry, Michelle R.
Source:
Environmental toxicology and chemistry 2019 v.38 no.5 pp. 1062-1073
ISSN:
0730-7268
Subject:
mechanism of action,   etc   ; data collection; databases; environmental assessment; information sources; risk assessment; toxicity; toxicity testing; vertebrates;     Show all 9 Subjects
Abstract:
... Flexible, rapid, and predictive approaches that do not require the use of large numbers of vertebrate test animals are needed because the chemical universe remains largely untested for potential hazards. Development of robust new approach methodologies and nontesting approaches requires the use of existing information via curated, integrated data sets. The ecological threshold of toxicological con ...
DOI:
10.1002/etc.4382

12. Development of a kinetic antibody-dependent cellular cytotoxicity assay

Author:
Kamen, Lynn; Thakurta, Tara; Myneni, Srividya; Zheng, Kai; Chung, Shan
Source:
Journal of immunological methods 2019 v.468 pp. 49-54
ISSN:
0022-1759
Subject:
mechanism of action,   etc   ; cytotoxicity; drugs; fluorescence; image analysis; in vitro studies; monoclonal antibodies; therapeutics; toxicity testing;     Show all 9 Subjects
Abstract:
... Antibody-dependent cellular cytotoxicity (ADCC) is an important mechanism of action (MOA) of monoclonal antibody (mAb) therapeutics. Target cells opsonized with therapeutic antibody bind and activate FcγR-bearing immune effector cells, resulting in target cell lysis. A key step in mAb drug development is the characterization of ADCC activity for its potential to inform mAb efficacy and safety. A n ...
DOI:
10.1016/j.jim.2019.02.006

13. Natural barrigenol–like triterpenoids: A comprehensive review of their contributions to medicinal chemistry

Author:
Zhang, Xinxin; Zhang, Song; Yang, Yiren; Wang, Da; Gao, Huiyuan
Source:
Phytochemistry 2019 v.161 pp. 41-74
ISSN:
0031-9422
Subject:
mechanism of action,   etc   ; Aesculus hippocastanum; Alzheimer disease; Xanthoceras sorbifolium; bioavailability; carbohydrates; moieties; pharmacokinetics; triterpenoids;     Show all 9 Subjects
Abstract:
... Barrigenol-like triterpenoids (BATs), which contain an unusual oleanane substituted by many hydroxyl groups as the skeleton, are subdivided into five subtypes: barrigenol A1, barrigenol A2, barrigenol R1, barringtogenol C, and 16-deoxybarringtogenol C. The variations in acyl derivatives, hydroxyl groups, and carbohydrate chains in their structures have enhanced the diversity of BATs. Moreover, the ...
DOI:
10.1016/j.phytochem.2019.01.017

14. Rab18: new insights into the function of an essential protein

Author:
Dejgaard, Selma Yilmaz; Presley, John F.
Source:
Cellular and molecular life sciences 2019 v.76 no.10 pp. 1935-1945
ISSN:
1420-682X
Subject:
mechanism of action,   etc   ; ancestry; autophagy; disease severity; droplets; endoplasmic reticulum; humans; lipids; proteins;     Show all 9 Subjects
Abstract:
... Rab18 is one of the small number of conserved Rab proteins which have been traced to the last eukaryotic common ancestor. It is found in organisms ranging from humans to trypanosomes, and localizes to multiple organelles, including most notably endoplasmic reticulum and lipid droplets. In humans, absence of Rab18 leads to a severe illness known as Warburg-Micro syndrome. Despite this evidence that ...
DOI:
10.1007/s00018-019-03050-3

15. Drug repurposing for new, efficient, broad spectrum antivirals

Author:
García-Serradilla, Moisés; Risco, Cristina; Pacheco, Beatriz
Source:
Virus research 2019 v.264 pp. 22-31
ISSN:
0168-1702
Subject:
mechanism of action,   etc   ; antiviral agents; disease outbreaks; drugs; human health; screening; therapeutics; vaccine development; viruses;     Show all 9 Subjects
Abstract:
... Emerging viruses are a major threat to human health. Recent outbreaks have emphasized the urgent need for new antiviral treatments. For several pathogenic viruses, considerable efforts have focused on vaccine development. However, during epidemics infected individuals need to be treated urgently. High-throughput screening of clinically tested compounds provides a rapid means to identify undiscover ...
DOI:
10.1016/j.virusres.2019.02.011

16. Dehydrocurvularin is a potent antineoplastic agent irreversibly blocking ATP-citrate lyase: evidence from chemoproteomics

Author:
Deng, Zhangshuang; Wong, Nai-Kei; Guo, Zhiyong; Zou, Kun; Xiao, Youli; Zhou, Yiqing
Source:
Chemical communications 2019 v.55 no.29 pp. 4194-4197
ISSN:
1364-548X
Subject:
mechanism of action,   etc   ; ATP citrate synthase; antineoplastic agents; chemical reactions; dehydrocurvularin;     Show all 5 Subjects
Abstract:
... Natural-product macrolide 10,11-dehydrocurvularin (DCV) was revealed to be a potent irreversible inhibitor of ATP-citrate lyase (ACLY) via classical chemoproteomic profiling, which mechanistically illuminates the anti-cancer mode of action of DCV and its analogues. ...
DOI:
10.1039/c9cc00256a

17. Effects of early enteral bovine colostrum supplementation on intestinal permeability in critically ill patients: A randomized, double-blind, placebo-controlled study

Author:
Eslamian, Ghazaleh; Ardehali, Seyed Hossein; Baghestani, Ahmad-Reza; Vahdat Shariatpanahi, Zahra
Source:
Nutrition 2019 v.60 pp. 106-111
ISSN:
0899-9007
Subject:
mechanism of action,   etc   ; adults; cow colostrum; diarrhea; endotoxins; intestines; patients; permeability; placebos;     Show all 9 Subjects
Abstract:
... In this study we sought to investigate the effect of early enteral bovine colostrum supplementation on intestinal permeability in intensive care unit (ICU)–hospitalized patients.A total of 70 ICU-hospitalized adult patients were randomly assigned to receive a bovine colostrum supplement or placebo according to the stratified blocked randomization by age and admission category. Plasma endotoxin and ...
DOI:
10.1016/j.nut.2018.10.013

18. Genome-wide Approaches to Investigate Anthelmintic Resistance

Author:
Doyle, Stephen R.; Cotton, James A.
Source:
Trends in parasitology 2019 v.35 no.4 pp. 289-301
ISSN:
1471-4922
Subject:
mechanism of action,   etc   ; anthelmintics; drug resistance; evolution; genes; high-throughput nucleotide sequencing; humans; livestock; parasites;     Show all 9 Subjects
Abstract:
... The rapid evolution of anthelmintic resistance in a number of parasites of livestock and domesticated animals has occurred in response to widespread use of anthelmintics for parasite control, and threatens the success of parasite control of species that infect humans. The genetic basis of resistance to most anthelmintics remains poorly resolved. Genome-wide approaches are now accessible due to rec ...
DOI:
10.1016/j.pt.2019.01.004

19. Long non-coding RNA in stem cell pluripotency and lineage commitment: functions and evolutionary conservation

Author:
Fico, Annalisa; Fiorenzano, Alessandro; Pascale, Emilia; Patriarca, Eduardo Jorge; Minchiotti, Gabriella
Source:
Cellular and molecular life sciences 2019 v.76 no.8 pp. 1459-1471
ISSN:
1420-682X
Subject:
mechanism of action,   etc   ; genome; humans; mice; non-coding RNA; rats; stem cells; transcription (genetics);     Show all 8 Subjects
Abstract:
... LncRNAs have recently emerged as new and fundamental transcriptional and post-transcriptional regulators acting at multiple levels of gene expression. Indeed, lncRNAs participate in a wide variety of stem cell and developmental processes, acting in cis and/or in trans in the nuclear and/or in the cytoplasmic compartments, and generating an intricate network of interactions with RNAs, enhancers, an ...
DOI:
10.1007/s00018-018-3000-z

20. The Eagle Effect and Antibiotic-Induced Persistence: Two Sides of the Same Coin?

Author:
Prasetyoputri, Anggia; Jarrad, Angie M.; Cooper, Matthew A.; Blaskovich, Mark A.T.
Source:
Trends in microbiology 2019 v.27 no.4 pp. 339-354
ISSN:
0966-842X
Subject:
mechanism of action,   etc   ; antibiotics; bacteria; cell death; fungi; in vivo studies; phenotype;     Show all 7 Subjects
Abstract:
... The Eagle effect describes a phenomenon in which bacteria or fungi exposed to concentrations of antibiotic higher than an optimal bactericidal concentration (OBC) have paradoxically improved levels of survival than at the OBC due to a decreased net rate of cell death. Despite extensive observational reports of this effect in different microorganisms, its underlying mode of action is not well under ...
DOI:
10.1016/j.tim.2018.10.007