A5052017771- Cancer therapeutics and mechanisms
- Effects and risks of endocrine disrupting chemicals
- Synthesis and biological activity
- Bioactive Compounds and Antitumor Agents
- Chemical Synthesis and Analysis
- Antibiotic Resistance in Bacteria
- Ion channel regulation and function
- Synthesis and Characterization of Heterocyclic Compounds
- Toxic Organic Pollutants Impact
- Estrogen and related hormone effects
- Click Chemistry and Applications
- Synthesis and Biological Evaluation
- Bacterial Genetics and Biotechnology
- Carcinogens and Genotoxicity Assessment
- Biochemical and Molecular Research
- Peptidase Inhibition and Analysis
- Chemistry and Chemical Engineering
- Cardiac electrophysiology and arrhythmias
- Bacteriophages and microbial interactions
- Quinazolinone synthesis and applications
- Computational Drug Discovery Methods
- Neutropenia and Cancer Infections
- Antibiotics Pharmacokinetics and Efficacy
- Phenothiazines and Benzothiazines Synthesis and Activities
- Nicotinic Acetylcholine Receptors Study
University of Ljubljana
2015-2024
Weatherford College
2012
Bacterial DNA gyrase and topoisomerase IV control the topological state of during replication are validated targets for antibacterial drug discovery. Starting from our recently reported 4,5,6,7-tetrahydrobenzo[1,2-d]thiazole-based B inhibitors, we replaced their central core with benzothiazole-2,6-diamine scaffold interchanged substituents in positions 2 6. This resulted equipotent nanomolar inhibitors Escherichia coli displaying improved inhibition Staphylococcus aureus both bacteria....
Environmental oestrogen bisphenol A (BPA) and its analogues are widespread in our living environment. Because their production use increasing, exposure of humans to bisphenols is becoming a significant issue. We evaluated the mutagenic genotoxic potential eight BPA structural (BPF, BPAF, BPZ, BPS, DMBPA, DMBPS, BP-1, BP-2) using Ames comet assay, respectively. None tested showed effect Salmonella typhimurium strains TA98 TA100 either presence or absence external S9-mediated metabolic...
Bacterial DNA gyrase and topoisomerase IV are essential enzymes that control the topological state of during replication validated antibacterial drug targets. Starting from a library marine alkaloid oroidin analogues, we identified low micromolar inhibitors Escherichia coli based on 5,6,7,8-tetrahydroquinazoline 4,5,6,7-tetrahydrobenzo[1,2-d]thiazole scaffolds. Structure-based optimization initial hits resulted in nanomolar E. inhibitors, some which exhibited inhibition Staphylococcus aureus...
Background: The endocrine disrupting chemical bisphenol A (BPA) has been facing stricter regulations in recent years. BPA analogs, such as the bisphenols S, F, and AF (BPS, BPF, BPAF) are increasingly used replacement chemicals, although they were found to exert estrogenic effects similar those of BPA. Research shown that only parent compounds have affinity estrogen receptors, suggesting pharmacokinetic behavior (BPs) can influence their potency. Objectives: Our goal was compare behaviors...
We have developed compounds with a promising activity against Acinetobacter baumannii and Pseudomonas aeruginosa, which are both on the WHO priority list of antibiotic-resistant bacteria. Starting from DNA gyrase inhibitor 1, we identified compound 27, featuring 10-fold improved aqueous solubility, inhibition topoisomerase IV A. P. decreased human IIα, no cross-resistance to novobiocin. Cocrystal structures 1 in complex Escherichia coli GyrB24 (S)-27 GyrB23 aeruginosa revealed their binding...
A new series of dual low nanomolar benzothiazole inhibitors bacterial DNA gyrase and topoisomerase IV were developed. The resulting compounds show excellent broad-spectrum antibacterial activities against Gram-positive Enterococcus faecalis, faecium multidrug resistant (MDR) Staphylococcus aureus strains [best compound minimal inhibitory concentrations (MICs): range, <0.03125–0.25 μg/mL] the Gram-negatives Acinetobacter baumannii Klebsiella pneumoniae (best MICs: 1–4 μg/mL). Lead 7a was...
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.
Endocrine disrupting chemicals such as natural and synthetic steroid hormones bisphenols are among the most important pollutants in aquatic environment. We performed an environmental chemical analysis of five Slovenian water samples, two rivers, one groundwater, influent effluent wastewater treatment plants, with a highly sensitive twenty-five endocrine-disrupting compounds belonging to groups hormones, bisphenols. Since these simultaneously present environment, it is study their individual...
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...
Marine organisms produce secondary metabolites that may be valuable for the development of novel drug leads as such and can also provide structural scaffolds design synthesis bioactive compounds. The marine alkaloids, clathrodin oroidin, which were originally isolated from sponges genus, Agelas, prepared evaluated their antimicrobial activity against three bacterial strains (Enterococcus faecalis, Staphylococcus aureus Escherichia coli) one fungal strain (Candida albicans), oroidin was found...
Bacterial DNA gyrase is a well-known and validated target in the design of antibacterial drugs. However, inhibitors its ATP binding subunit, B (GyrB), have so far not reached clinical use. In present study, three different series N-phenyl-4,5-dibromopyrrolamides N-phenylindolamides were designed prepared as potential inhibitors. The IC50 values compounds on from Escherichia coli low micromolar range, with best compound, (4-(4,5-dibromo-1H-pyrrole-2-carboxamido)benzoyl)glycine (18a),...