Search results for " Pharmaceutic"
showing 10 items of 865 documents
The Role of Statins on Helicobacter pylori Eradication: Results from the European Registry on the Management of H. pylori (Hp-EuReg)
2021
Statins could increase the effectiveness of Helicobacter pylori eradication therapies due to their anti-inflammatory effect. The aim of this study was to analyze the impact of this therapeutic association in real life. This is a multicenter, prospective, non-interventional study aimed at evaluating the management of H. pylori by European gastroenterologists. Patients were registered in an e-CRF by AEG-REDCap from 2013 to 2020. The association between statin use and H. pylori eradication effectiveness was evaluated through multivariate analysis. Overall, 9988 and 705 patients received empirical and culture-guided treatment, respectively. Overall, statin use was associated with higher effecti…
Role of D-Mannose in the Prevention of Recurrent Uncomplicated Cystitis: State of the Art and Future Perspectives
2021
Background: Urinary tract infections (UTI) are highly frequent in women, with a significant impact on healthcare resources. Although antibiotics still represent the standard treatment to manage recurrent UTI (rUTI), D-mannose, an inert monosaccharide that is metabolized and excreted in urine and acts by inhibiting bacterial adhesion to the urothelium, represents a promising nonantibiotic prevention strategy. The aim of this narrative review is to critically analyze clinical studies reporting data concerning the efficacy and safety of D-mannose in the management of rUTIs. Methods: A non-systematic literature search, using the Pubmed, EMBASE, Scopus, Web of science, Cochrane Central Register …
Adapting a Phage to Combat Phage Resistance
2020
Phage therapy is becoming a widely recognized alternative for fighting pathogenic bacteria due to increasing antibiotic resistance problems. However, one of the common concerns related to the use of phages is the evolution of bacterial resistance against the phages, putatively disabling the treatment. Experimental adaptation of the phage (phage training) to infect a resistant host has been used to combat this problem. Yet, there is very little information on the trade-offs of phage infectivity and host range. Here we co-cultured a myophage FCV-1 with its host, the fish pathogen Flavobacterium columnare, in lake water and monitored the interaction for a one-month period. Phage resistance was…
Bioaccumulation of emerging contaminants in mussel (Mytilus galloprovincialis): Influence of microplastics
2021
Coastal environments are heavily influenced by human activities. Chemical substances considered as emerging contaminants (ECs) are one of the most important indicators of the anthropic influence on the environment, and they have recently shown to interact with microplastics (MPs). Mussels are suitable for in-lab bioacumulation studies providing insight about the occurrence and fate of contaminants in the organisms. In this study, bioacummulation of 20 chemical substances catalogued as ECs, including pharmaceuticals and personal care products (PPCPs), pesticides, and perfluoroalkyl substances (PFASs) in Mytilus galloprovincialis was assessed, with or without the influence of the presence of …
Pharmacophore Models Derived from Molecular Dynamics Simulations of Protein-Ligand Complexes: A Case Study
2018
A single, merged pharmacophore hypothesis is derived combining 2000 pharmacophore models obtained during a 20 ns molecular dynamics simulation of a protein-ligand complex with one pharmacophore model derived from the initial PDB structure. This merged pharmacophore model contains all features that are present during the simulation and statistical information about the dynamics of the pharmacophore features. Based on the dynamics of the pharmacophore features we derive two distinctive feature patterns resulting in two different pharmacophore models for the analyzed system – the first model consists of features that are obtained from the PDB structure and the second uses two features that ca…
The Repurposing of Old Drugs or Unsuccessful Lead Compounds by in Silico Approaches: New Advances and Perspectives
2015
Have you a compound in your lab, which was not successful against the designed target, or a drug that is no more attractive? The drug repurposing represents the right way to reconsider them. It can be defined as the modern and rationale approach of the traditional methods adopted in drug discovery, based on the knowledge, insight and luck, alias known as serendipity. This repurposing approach can be applied both in silico and in wet. In this review we report the molecular modeling facilities that can be of huge support in the repurposing of drugs and/or unsuccessful lead compounds. In the last decades, different methods were proposed to help the scientists in drug design and in drug repurpo…
Reaction between Indazole and Pd-Bound Isocyanides-A Theoretical Mechanistic Study
2018
The mechanism of the addition of indazole (Ind)&mdash
An Experimental Toolbox for Structure‐Based Hit Discovery for P. aeruginosa FabF, a Promising Target for Antibiotics
2021
Abstract FabF (3‐oxoacyl‐[acyl‐carrier‐protein] synthase 2), which catalyses the rate limiting condensation reaction in the fatty acid synthesis II pathway, is an attractive target for new antibiotics. Here, we focus on FabF from P. aeruginosa (PaFabF) as antibiotics against this pathogen are urgently needed. To facilitate exploration of this target we have set up an experimental toolbox consisting of binding assays using bio‐layer interferometry (BLI) as well as saturation transfer difference (STD) and WaterLOGSY NMR in addition to robust conditions for structure determination. The suitability of the toolbox to support structure‐based design of FabF inhibitors was demonstrated through the …
Inhibitors of inducible NO synthase expression: total synthesis of (S)-curvularin and its ring homologues.
2008
(S)-Curvularin and its 13-, 14-, and 16-membered lactone homologues were synthesized through a uniform strategy in which a Kochi oxidative decarboxylation and ring-closing metathesis reactions constitute the key processes. In the evaluation of the anti-inflammatory effects of the synthesized compounds in assays using cells stably transfected with a human iNOS promoter-luciferase reporter gene construct, the 14- and 16-membered homologues showed a slightly higher inhibitory effect towards iNOS promoter activity than curvularin itself. However, the larger ring homologues also exhibited higher cytotoxicity, manifest in downregulated eNOS promoter activity. In contrast, the di-O-acetyl and 4-ch…
Optimization of Triazine Nitriles as Rhodesain Inhibitors: Structure-Activity Relationships, Bioisosteric Imidazopyridine Nitriles, and X-ray Crystal…
2013
The cysteine protease rhodesain of Trypanosoma brucei parasites causing African sleeping sickness has emerged as a target for the development of new drug candidates. Based on a triazine nitrile moiety as electrophilic headgroup, optimization studies on the substituents for the S1, S2, and S3 pockets of the enzyme were performed using structure-based design and resulted in inhibitors with inhibition constants in the single-digit nanomolar range. Comprehensive structure-activity relationships clarified the binding preferences of the individual pockets of the active site. The S1 pocket tolerates various substituents with a preference for flexible and basic side chains. Variation of the S2 subs…