A5005492881- Drug Transport and Resistance Mechanisms
- Enzyme function and inhibition
- Cancer therapeutics and mechanisms
- HIV/AIDS drug development and treatment
- Synthesis and Catalytic Reactions
- Phenothiazines and Benzothiazines Synthesis and Activities
- Chemical Reaction Mechanisms
- Antibiotic Resistance in Bacteria
- Analytical Chemistry and Chromatography
- Synthesis and Biological Evaluation
- Mass Spectrometry Techniques and Applications
- Metal complexes synthesis and properties
- Antibiotics Pharmacokinetics and Efficacy
- Receptor Mechanisms and Signaling
- Analytical Methods in Pharmaceuticals
- Bioactive Compounds and Antitumor Agents
- Pharmacological Effects and Toxicity Studies
- Metabolism, Diabetes, and Cancer
- Pharmacological Receptor Mechanisms and Effects
- Chemical Synthesis and Analysis
- DNA and Nucleic Acid Chemistry
- Bacterial Genetics and Biotechnology
- Metabolomics and Mass Spectrometry Studies
- Pancreatic function and diabetes
- Nicotinic Acetylcholine Receptors Study
University of Florence
2019-2025
Piperazine is a structural element present in drugs belonging to various chemical classes and used for numerous different therapeutic applications; it has been considered privileged scaffold drug design.The authors have searched examples of piperazine-containing compounds among recently approved by the FDA some research fields (nicotinic receptor modulators, acting against cancer, bacterial multidrug resistance), looking particular design behind insertion this moiety.Piperazine widely due...
The piperazine moiety is often found in drugs or bioactive molecules. This widespread presence due to different possible roles depending on the position molecule and therapeutic class, but it also depends chemical reactivity of piperazine-based synthons, which facilitate its insertion into molecule. In this paper, we take consideration piperazine-containing approved by Food Drug Administration between January 2011 June 2023, synthetic methodologies used prepare compounds discovery process...
A new series of N,N-bis(alkanol)amine aryl diesters was synthesized and studied as dual P-glycoprotein (P-gp) carbonic anhydrase XII inhibitors (CA XII). These hybrids should be able to synergistically overcome P-gp mediated multidrug resistance (MDR) in cancer cells. It reported that the efflux activity could modulated by CA XII, pH reduction caused inhibition produces a significant decrease ATPase activity. The compounds here feature both binding moieties. contain diester scaffold found...
In a continuing search of dual P-gp and hCA XII inhibitors, we synthesized studied new N,N-bis(alkanol)amine aryl diester derivatives characterized by the presence coumarin group. These hybrids contain both binding groups to synergistically overcome P-gp-mediated multidrug resistance (MDR) in cancer cells expressing XII. Indeed, modulates efflux activity inhibition reduces intracellular pH, thereby decreasing ATPase P-gp. All compounds showed inhibitory activities on proteins taken...
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The tandem mass spectrometry (MS/MS) approach employing an ion trap analyzer (IT) was evaluated in isomers recognition. proposed consists of sole, simple, and rapid liquid chromatographic separation (HPLC) without requiring resolution between the analytes. Then, MS/MS properties were optimized to solve signal assignment using post-processing data elaboration (LEDA). IT-MS/MS experiment uses same site, helium as collision gas, different time steps modify applied conditions on studied ions....
New 2,5- and 1,5-disubstituted tetrazoles, 2,5-disubstituted-1,3,4-oxadiazoles were synthesized as tariquidar elacridar derivatives studied multidrug resistance (MDR) reversers. Their behaviour on the three ABC transporters P-gp, MRP1 BCRP was investigated. All compounds inhibited P-gp transport activity in MDCK-MDR1 cells overexpressing showing EC50 values even low nanomolar range (compounds 15, 22). Oxadiazole able to increase antiproliferative effect of doxorubicin HT29/DX confirming...
Some 2,4-disubstituted quinazolines were synthesized and studied as multidrug resistance (MDR) reversers. The new derivatives carried the quinazoline-4-amine scaffold found in modulators of ABC transporters involved MDR, TKIs gefitinib erlotinib. Their behaviour on three transporters, P-gp, MRP1 BCRP, was investigated. Almost all compounds inhibited P-gp activity MDCK-MDR1 cells overexpressing showing EC
A new series of piperazine derivatives were synthesized and studied with the aim obtaining dual inhibitors P-glycoprotein (P-gp) carbonic anhydrase XII (hCA XII) to synergistically overcome P-gp-mediated multidrug resistance (MDR) in cancer cells expressing two proteins, P-gp hCA XII. Indeed, these hybrid compounds contain both binding groups on nitrogen atoms heterocyclic ring. All showed good inhibitory activity each protein (P-gp individually, many them a synergistic effect resistant...
This paper proposes a tandem mass spectrometry (MS/MS) approach in isomer recognition by playing the "energetic dimension" of experiment. The chromatographic set up (HPLC) was tuned to minimize run time, without requiring high efficiency or resolution between isomers. Then, MS/MS properties were explored solve signal assignment performing series energy resolved experiments order optimize parameters, and applying an interesting post-processing data elaboration tool (LEDA). reliability new...
The Carbonic Anhydrase (CA, EC 4.2.1.1) activating properties of histamine have been known for a long time. This compound has extensively modified but only in few instances the imidazole ring replaced with other heterocycles. It was envisaged that imidazoline could be bioisoster moiety. Indeed, we report clonidine, 2-aminoimidazoline derivative, found able to activate several human CA isoforms (hCA I, IV, VA, VII, IX, XII and XIII), potency micromolar range, while it inactive on hCA II. A...
Aim: To investigate the action mechanism of 1-benzyl-1,4-diazepane (1-BD) as efflux pump inhibitor (EPI) in Escherichia coli mutants: ΔacrAB or overexpressing AcrAB and AcrEF pumps. Materials & methods: Effect 1-BD on: antibiotic potentiation, by microdilution method; membrane functionality, fluorimetric assays; ethidium bromide accumulation, fluorometric real-time assay; AcrB expression, quantitative photoactivated localization microscopy. Results: decreases minimal inhibitory concentration...
MDR in bacteria is threatening to public health. Overexpression of efflux pumps an important cause MDR. The co-administration antimicrobial drugs and pump inhibitors (EPIs) a promising approach address the problem MDR.To identify new putative EPIs characterize their mechanisms action.The effects four selected piperazine derivatives on resistance-nodulation-cell division (RND) was evaluated Escherichia coli strains overexpressing or not expressing RND by assays aimed at evaluating antibiotic...
A series of histamine (HST)-related compounds were synthesized and tested for their activating properties on five physiologically relevant human Carbonic Anhydrase (hCA) isoforms (I, II, Va, VII XIII). The imidazole ring HST was replaced with different 5-membered heterocycles the length aliphatic chain varied. For most interesting some modifications terminal amino group also performed. sensitive isoform to activation hCA I (KA values in low micromolar range), but surprisingly none new...
Metformin is the most prescribed glucose-lowering drug worldwide; globally, over 100 million patients are this annually. Some different action mechanisms have been proposed for drug, but, surprisingly, no metabolite of metformin has ever described. It was considered interesting to investigate possible reaction with glucose following Maillard pattern. The first performed in vitro conditions, showing formation two adducts that originated by condensation molecular species losses one or water...