A5067176307- Computational Drug Discovery Methods
- Microbial Natural Products and Biosynthesis
- Aldose Reductase and Taurine
- Enzyme Structure and Function
- Cancer therapeutics and mechanisms
- Bacterial Genetics and Biotechnology
- Estrogen and related hormone effects
- Click Chemistry and Applications
- Antibiotic Resistance in Bacteria
- Protease and Inhibitor Mechanisms
- Protein Structure and Dynamics
- Machine Learning in Bioinformatics
- Synthesis and Characterization of Heterocyclic Compounds
- Pneumonia and Respiratory Infections
- Bacteriophages and microbial interactions
- Hormonal Regulation and Hypertension
- Peptidase Inhibition and Analysis
- Glycosylation and Glycoproteins Research
- Hormonal and reproductive studies
- Chemical Synthesis and Analysis
- Machine Learning in Materials Science
- Synthesis and biological activity
- Biochemical and Molecular Research
- Prenatal Substance Exposure Effects
- Eicosanoids and Hypertension Pharmacology
BioMed X Institute
2014-2018
University of Ljubljana
2008-2015
Inspired by natural language processing techniques, we here introduce Mol2vec, which is an unsupervised machine learning approach to learn vector representations of molecular substructures. Like the Word2vec models, where vectors closely related words are in close proximity space, Mol2vec learns substructures that point similar directions for chemically Compounds can finally be encoded as summing individual and, instance, fed into supervised approaches predict compound properties. The...
Annotations of the phylogenetic tree human kinome is an intuitive way to visualize compound profiling data, structural features kinases or functional relationships within this important class proteins. The increasing volume and complexity kinase-related data underlines need for a tool that enables complex queries pertaining kinase disease involvement potential therapeutic uses inhibitors.Here, we present KinMap, user-friendly online facilitates interactive navigation through knowledge by...
Butyrylcholinesterase (BChE) is regarded as a promising drug target its levels and activity significantly increase in the late stages of Alzheimer’s disease. To discover novel BChE inhibitors, we used hierarchical virtual screening protocol followed by biochemical evaluation 40 highest scoring hit compounds. Three compounds identified showed significant inhibitory activities against BChE. The most potent, compound 1 (IC50 = 21.3 nM), was resynthesized resolved into pure enantiomers. A high...
Predicting the endocrine disruption potential of compounds is a daunting but essential task. Here we report new tool for this purpose that have termed Endocrine Disruptome. It free and simple-to-use Web service runs on an open source platform called Docking interface Target Systems (DoTS). The molecular docking handled via AutoDock Vina. Compounds are docked to 18 integrated well-validated crystal structures 14 different human nuclear receptors: androgen receptor; estrogen receptors α β;...
Kinome-wide screening would have the advantage of providing structure-activity relationships against hundreds targets simultaneously. Here, we report generation ligand-based activity prediction models for over 280 kinases by employing Machine Learning methods on an extensive data set proprietary bioactivity combined with open data. High quality (AUC > 0.7) was achieved ∼200 (1) combining data, (2) choosing Random Forest alternative tested methods, and (3) balancing training sets. Tests...
We have designed, synthesized, and evaluated 5-benzylidenerhodanine- 5-benzylidenethiazolidine-2,4-dione-based compounds as inhibitors of bacterial enzyme MurD with E. coli IC50 in the range 45−206 μM. The high-resolution crystal structure complex (R,Z)-2-(3-[{4-([2,4-dioxothiazolidin-5-ylidene]methyl)phenylamino}methyl)benzamido)pentanedioic acid [(R)-32] revealed details binding mode inhibitor within active site provides a good foundation for structure-based design novel generation inhibitors.
Aims CYP53A15, from the sorghum pathogen Cochliobolus lunatus, is involved in detoxification of benzoate, a key intermediate aromatic compound metabolism fungi. Because this enzyme unique to fungi, it promising drug target fungal pathogens other eukaryotes. Methods and Results In our work, we showed high antifungal activity seven cinnamic acid derivatives against C. lunatus two Aspergillus niger Pleurotus ostreatus. To elucidate mechanism action with most potent properties, studied...
A new trick for an old dog! Aberrant cathepsin B activity is associated with tumor progression, however, despite extensive research, there are no inhibitors in clinical use. Here, nitroxoline, established antimicrobial agent, identified as a potent, reversible inhibitor of B, and thus potential drug candidate the treatment cancer other diseases which plays role.
Inspired by natural language processing techniques we here introduce Mol2vec which is an unsupervised machine learning approach to learn vector representations of molecular substructures. Similarly, the Word2vec models where vectors closely related words are in close proximity space, learns substructures that pointing similar directions for chemically Compounds can finally be encoded as summing up individual and, instance, feed into supervised approaches predict compound properties. The...
Mur ligases participate in the intracellular path of bacterial peptidoglycan biosynthesis and constitute attractive, although so far underexploited, targets for antibacterial drug discovery. A series hydroxy-substituted 5-benzylidenethiazolidin-4-ones were synthesized tested as inhibitors ligases. The most potent compound 5 a was active against MurD-F with IC(50) values between 2 6 microm, making it promising multitarget inhibitor Antibacterial activity different strains, inhibitory protein...
Mycobacterial enoyl acyl carrier protein reductase (InhA) is a clinically validated target for the treatment of tuberculosis infections, disease that still causes death at least million people annually. A known class potent, direct, and competitive InhA inhibitors based on tetracyclic thiadiazole structure has been shown to have in vivo activity murine models infection. On basis this template, we here explored medicinal chemistry truncated analogues only three aromatic rings. In particular,...
17β-Hydroxysteroid dehydrogenase type 1 (17β-HSD1) is an enzyme that catalyzes NADPH-dependent reduction of the weak estrogen, estrone, into most potent estradiol, which exerts proliferative effects via estrogen receptors. Overexpression 17β-HSD1 in estrogen-responsive tissues related to development hormone-dependent diseases, such as breast cancer and endometriosis; thus, represents attractive target for new therapies. We have discovered simple coumarines 2 significantly inhibit a...
Protein kinases are involved in a variety of diseases including cancer, inflammation, and autoimmune disorders. Although the development new kinase inhibitors is major focus pharmaceutical research, large number remained so far unexplored drug discovery projects. The selection assessment targets an essential but challenging area. Today, few thousands experimentally determined structures available, covering about half human kinome. This structural source allows guiding target via...
Background Penicillin-binding proteins (PBPs) are well known and validated targets for antibacterial therapy. The most important clinically used inhibitors of PBPs β-lactams inhibit transpeptidase activity by forming a covalent penicilloyl-enzyme complex that blocks the normal transpeptidation reaction; this finally results in bacterial death. In some resistant bacteria resistance is acquired active-site distortion PBPs, which lowers their acylation efficiency β-lactams. To address problem...
The identification and design of selective compounds is important for the reduction unwanted side effects as well development tool target validation studies. This is, in particular, true therapeutically protein families that possess conserved folds have numerous members such kinases. To support kinase inhibitors, we developed a novel approach allows specificity determining subpockets between closely related kinases solely based on their three-dimensional structures. account intrinsic...
Cinnamic acid derivatives can be found in plant material, and they possess a remarkable variety of biological effects. In the present study, we have investigated cytotoxic effects representative cinnamic esters amides. The cytotoxicity was determined by MTT test on human cervix adenocarcinoma (HeLa), myelogenous leukemia (K562), malignant melanoma (Fem-x), estrogen-receptor-positive breast cancer (MCF-7) cells, versus peripheral blood mononuclear cells (PBMCs) without or with addition lectin...