A5085025902- Synthesis and biological activity
- Synthesis and Biological Evaluation
- Inflammatory mediators and NSAID effects
- Click Chemistry and Applications
- Cancer therapeutics and mechanisms
- Receptor Mechanisms and Signaling
- Computational Drug Discovery Methods
- Epigenetics and DNA Methylation
- Cell death mechanisms and regulation
- Asthma and respiratory diseases
- Synthesis of β-Lactam Compounds
- Bioactive Compounds and Antitumor Agents
- Synthetic Organic Chemistry Methods
- Synthesis and Characterization of Heterocyclic Compounds
- Microtubule and mitosis dynamics
- Hedgehog Signaling Pathway Studies
- Muscle Physiology and Disorders
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Antiplatelet Therapy and Cardiovascular Diseases
- Synthesis of heterocyclic compounds
- Plant-derived Lignans Synthesis and Bioactivity
- Histone Deacetylase Inhibitors Research
- CRISPR and Genetic Engineering
- Immune responses and vaccinations
CHDI Foundation
2010-2021
Torrey Pines Institute For Molecular Studies
2018
Moscow Institute of Physics and Technology
2013-2016
N.D. Zelinsky Institute of Organic Chemistry
2007-2014
ChemDiv (United States)
2005-2013
deCODE Genetics (Iceland)
2008-2010
Chemical Diversity Research Institute
2006
We describe a novel fragment library termed fragments of life (FOL) for structure-based drug discovery. The FOL includes natural small molecules life, derivatives thereof, and biaryl protein architecture mimetics. choice facilitates the interrogation active sites, allosteric binding protein−protein interaction surfaces binding. screened against leukotriene A4 hydrolase (LTA4H) by X-ray crystallography. A diverse set including resveratrol, nicotinamide, indole were identified as efficient...
A series of both novel and reported combretastatin analogues, including diarylpyrazoles, -isoxazoles, -1,2,3-triazoles, -pyrroles, were synthesized via improved protocols to evaluate their antimitotic antitubulin activity using in vivo sea urchin embryo assay a panel human cancer cells. systematic comparative structure-activity relationship studies these compounds conducted. Pyrazoles 1i 1p, isoxazole 3a, triazole 7b found be the most potent antimitotics across all tested causing cleavage...
Myocardial infarction and stroke are caused by blood clots forming over a ruptured or denuded atherosclerotic plaque (atherothrombosis). Production of prostaglandin E2 (PGE2) an inflamed exacerbates atherothrombosis may limit the effectiveness current therapeutics. Platelets express multiple G-protein coupled receptors, including receptors for ADP PGE2. can mobilize Ca2+ through P2Y12 receptor inhibit cAMP production, causing platelet activation aggregation. Clopidogrel (Plavix), selective...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of Antimitotic Polyalkoxyphenyl Derivatives Combretastatin Using Plant Allylpolyalkoxybenzenes (1)Victor V. Semenov*†‡, Alex S. Kiselyov§, Ilia Y. Titov†, Irina K. Sagamanova†, Natalie N. Ikizalp§, Natalia B. Chernysheva†, Dmitry Tsyganov†, Leonid D. Konyushkin†, Sergei I. Firgang†, Roman Semenov†, Karmanova†, Mikhail M. Raihstat†, and Marina Semenova‡⊥View Author Information Zelinsky Institute Organic Chemistry RAS, 47 Leninsky Prospect,...
Both in-house human genetic and literature data have converged on the identification of leukotriene 4 hydrolase (LTA4H) as a key target for treatment cardiovascular disease. We combined fragment-based crystallography screening with an iterative medicinal chemistry effort to optimize inhibitors LTA4H. Ligand efficiency was followed throughout our structure−activity studies. As applied within context LTA4H inhibitor design, team able design potent compound 20 (DG-051) (Kd = 26 nM) high aqueous...
A series of 4-azapodophyllotoxin derivatives with modified rings B and E have been synthesized using allylpolyalkoxybenzenes from parsley seed oil. The targeted molecules were evaluated in vivo a phenotypic sea urchin embryo assay for antimitotic tubulin destabilizing activity. most active compounds identified by the featured myristicin-derived ring (4e, 6e, 8e). These determined to be more potent than podophyllotoxin. Cytotoxic effects selected further confirmed conventional assays A549...
Skeletal muscle myoblasts (iMyoblasts) were generated from human induced pluripotent stem cells (iPSCs) using an efficient and reliable transgene-free induction cell selection protocol. Immunofluorescence, flow cytometry, qPCR, digital RNA expression profiling, scRNA-Seq studies identify iMyoblasts as a PAX3+/MYOD1+ skeletal myogenic lineage with fetal-like transcriptome signature, distinct adult biopsy (bMyoblasts) iPSC-induced progenitors. can be stably propagated for >12 passages or 30...
We have synthesized a series of novel cis-restricted 4,5-polyalkoxydiaryl-3-aminopyrazole analogues combretastatins via short synthetic sequences using building blocks isolated from dill and parsley seed extracts. The resulting compounds were tested in vivo the phenotypic sea urchin embryo assay to reveal their antimitotic antitubulin effects. most potent aminopyrazole, 14a, altered embryonic cell division at 10 nM concentration, exhibiting microtubule-destabilizing properties. Compounds 12a...
Abstract Huntington’s disease (HD) is caused by a CAG trinucleotide repeat expansion in the first exon of huntingtin ( HTT ) gene coding for (HTT) protein. The misfolding and consequential aggregation CAG-expanded mutant (mHTT) underpin HD pathology. Our interest life cycle led us to consider development high-affinity small-molecule binders oligomerized/amyloid-containing species that could serve as either cellular vivo imaging tools or potential therapeutic agents. We recently reported PET...
The EP(3) receptor on the platelet mediates prostaglandin E(2) potentiation of thrombogenic coagonists including collagen and adenosine diphosphate (ADP). A pharmacophore driven approach led to identification diverse peri-substituted heterocycles as potent selective antagonists. simultaneous chemical optimization druglike assessment prioritized molecules converged a lead compound 50 (DG-041) that displayed favorable in vitro functional activities an inhibitor human aggregation. This agent is...
Through medicinal chemistry lead optimization studies focused on calculated properties and guided by X-ray crystallography computational modeling, potent pan-JNK inhibitors were identified that showed submicromolar activity in a cellular assay. Using vitro ADME profiling data, 9t was as possessing favorable permeability low potential for efflux, but it rapidly cleared liver microsomal incubations. In mouse pharmacokinetics study, compound brain-penetrant after oral dosing, exposure limited...
A concise six-step protocol for the synthesis of isoflavone glaziovianin (GVA) and its alkoxyphenyl derivatives 9 starting with readily available plant metabolites from dill parsley seeds was developed. The reaction sequence involved an efficient conversion key intermediate epoxides 7 into respective β-ketoaldehydes 8 followed by their Cu(I)-mediated cyclization target series 9. biological activity GVA evaluated using a panel seven human cancer cell lines in vivo sea urchin embryo assay....