A5003605275- Biochemical and Molecular Research
- Cancer therapeutics and mechanisms
- Synthesis and Reactivity of Heterocycles
- Chemical Synthesis and Analysis
- Microbial Natural Products and Biosynthesis
- Antimicrobial Peptides and Activities
- X-ray Diffraction in Crystallography
- Synthesis and Biological Evaluation
- Asymmetric Synthesis and Catalysis
- Crystallization and Solubility Studies
- Synthesis and biological activity
- Vitamin D Research Studies
- Receptor Mechanisms and Signaling
- HIV/AIDS drug development and treatment
- Protein Kinase Regulation and GTPase Signaling
- Quinazolinone synthesis and applications
- Synthesis and Characterization of Heterocyclic Compounds
- Antimicrobial Resistance in Staphylococcus
- Genomics and Phylogenetic Studies
- Chemical synthesis and alkaloids
- Advanced Synthetic Organic Chemistry
- Click Chemistry and Applications
- Phenothiazines and Benzothiazines Synthesis and Activities
- Radiopharmaceutical Chemistry and Applications
- HER2/EGFR in Cancer Research
Rega Institute for Medical Research
2006-2024
KU Leuven
2010-2024
Medicina
2016
Interface Europe (Belgium)
2013
Ghent University
2001-2004
Università degli Studi del Piemonte Orientale “Amedeo Avogadro”
2002
Tecnologie Avanzate (Italy)
2002
Henan Academy of Sciences
1999
Serratia plymuthica strain RVH1, initially isolated from an industrial food processing environment, displays potent antimicrobial activity towards a broad spectrum of Gram-positive and Gram-negative bacterial pathogens. Isolation subsequent structure determination bioactive molecules led to the identification two polyamino antibiotics with same molecular as zeamine II well third, closely related analogue, designated I. The gene cluster encoding biosynthesis was cloned sequenced shown encode...
There are currently no approved drugs for the treatment of emerging viral infections, such as dengue and Ebola. Adaptor-associated kinase 1 (AAK1) is a cellular serine-threonine protein that functions key regulator clathrin-associated host adaptor proteins regulates intracellular trafficking multiple unrelated RNA viruses. Moreover, AAK1 overexpressed specifically in virus-infected but not bystander cells. Because promising antiviral drug target, we have embarked on an optimization campaign...
DRAK2 emerged as a promising drug target for the treatment of autoimmune diseases and to prevent graft rejection after organ transplantation. Screening compound library in binding assay led identification an isothiazolo[5,4-b]pyridine derivative novel ligand DRAK2, displaying Kd value 1.6 μM. Subsequent medicinal chemistry work discovery thieno[2,3-b]pyridine with strong affinity (Kd = 9 nM). Moreover, this also behaves functional inhibitor enzymatic activity, IC50 0.82 μM, although lacking...
Herein we describe the synthesis and in vitro vivo activity of thiazolo[5,4-d]pyrimidines as a novel class immunosuppressive agents, useful for preventing graft rejection after organ transplantation. This research resulted discovery series compounds with potent mixed lymphocyte reaction (MLR) assay, which is well-known model The most congeners displayed IC(50) values less than 50 nM this MLR assay hence are equipotent to cyclosporin A, clinically used drug. One representative was further...
Abstract The enoyl‐acyl carrier protein reductase enzyme FabI is essential for fatty acid biosynthesis in Staphylococcus aureus and represents a promising target the development of novel, urgently needed anti‐staphylococcal agents. Here, we elucidate mode action kalimantacin antibiotics, novel class inhibitors with clinically‐relevant activity against multidrug‐resistant S. . By combining X‐ray crystallography molecular dynamics simulations, vitro kinetic studies chemical derivatization...
A novel series of analogs 1,25-dihydroxyvitamin D3, the hormonally active metabolite vitamin characterised by presence a trans-fused decalin CD-ring system, possesses surprising biological activities in combination with specific structural modifications flexible parts molecule, when compared natural hydrindane derivatives. (1) large difference activity is observed between 20-epimeric trans-decalin that follows pattern opposite to what usually for ring size. (2) Several are modified...
Abstract In recent years, DAPK‐related apoptosis‐inducing protein kinase 2 (DRAK2) has emerged as a promising target for the treatment of variety autoimmune diseases and prevention graft rejection after organ transplantation. However, medicinal chemistry optimization campaigns discovery novel small‐molecule inhibitors DRAK2 have not yet been published. Screening proprietary compound library led to benzothiophene analogue that displays an affinity constant ( K d ) value 0.25 μ M . Variation...
The primary target of a novel series immunosuppressive 7-piperazin-1-ylthiazolo[5,4- d]pyrimidin-5-amines was identified as the lipid kinase, PI4KIIIβ. Evaluation highlighted their poor solubility and unwanted off-target activities. A medicinal chemistry strategy put in place to optimize physicochemical properties within series, while maintaining potency improving selectivity over other kinases. Compound 22 initially profiled vivo, before further modifications led discovery 44 (UCB9608),...
A new method for the construction of (aryloxy)phosphoramidate nucleoside prodrugs is presented. An ribose derivative as key building block was used coupling with a number nucleobases under Vorbrüggen reaction conditions yielding protected ProTides in excellent yields. Selective hydrolysis acetoxy groups on sugar moiety afforded series desired ProTides. The advantage this approach, when compared to classical procedures, greater flexibility achieving structural variety nucleobase moiety.
Abstract The synthesis of a pyrido[4,3‐ d ]pyrimidine library from 4,6‐diamino‐2‐bromonicotinamide and 4,6‐diaminonicotinamide is described. A systematic variation the substituents at positions 2, 4, 5 7 scaffold was carried out, leading to wide variety structural analogues. This strategy led discovery new class PDE‐4 inhibitors. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Elevated production of tumor necrosis factor (TNF) plays a central role in the pathogenesis many inflammatory diseases, such as rheumatoid arthritis and Crohn's disease. Naturally occurring pteridine analogs have been reported to potent immunomodulatory activity, especially on TNF production. The aim this study is identify small molecule inhibitiors derived from prove their vivo efficacy an model. A focused chemical library based scaffold was screened vitro lipopolysaccharide (LPS)-induced...
[reaction: see text]. The IMDA reaction of 9 leads with good stereoselectivity to exo-adduct 10b. functionalized ABC-ring core in 10 is well suited for the convergent synthesis analogues himbacine, a naturally occurring M2 selective muscarine receptor antagonist, as illustrated further dehydro-derivative 5.
Abstract The enoyl‐acyl carrier protein reductase enzyme FabI is essential for fatty acid biosynthesis in Staphylococcus aureus and represents a promising target the development of novel, urgently needed anti‐staphylococcal agents. Here, we elucidate mode action kalimantacin antibiotics, novel class inhibitors with clinically‐relevant activity against multidrug‐resistant S. . By combining X‐ray crystallography molecular dynamics simulations, vitro kinetic studies chemical derivatization...
In an attempt to identify novel nucleoside phosphoramidate analogues for improving the anti-HCV activity of 2'-C-Me-uridine, we have synthesized first time a series l-glutamic acid, l-serine, l-threonine and l-tyrosine containing aryloxyphosphoramidate prodrugs 2'-C-Me-uridine. Evaluation their against HCV revealed that they displayed very potent activity, with EC50 values are in same range as Sofosbuvir.