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1.
Environ Sci Pollut Res Int ; 30(49): 107878-107886, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37740162

ABSTRACT

The study about how tyre-derived particles can potentially worsen the water quality and how traffic pollution markers can affect the environment is crucial for environmental management. Road emissions are known to contribute to pollution in various environments, and benzothiazoles and their derivates can be used to trace pollutant inputs related to surface runoff in the aquatic system. A total of eight benzothiazoles were determined in highway stormwater runoff and road dust collected from February to August 2022 near Venice (Casale sul Sile, Veneto Region, Italy). A new analytical method was validated, by using an UHPLC system coupled to a mass spectrometer (triple quadrupole). The target compounds were determined in both dissolved phase and suspended particulate matter of runoff, and the road dust samples were divided into seven fractions depending on particle diameters to understand the fraction partitioning. The results indicate that 2-SO3H-BTH was the most concentrated benzothiazole in all the analysed substrates, suggesting tyre debris as the main source because it is usually used in the vulcanization process. 2-SO3H-BTH reached a mean concentration of 115 ± 59 µg L-1, 4 ± 3 µg L-1, and 411 ± 441 µg Kg-1 for dissolved phase, suspended particulate matter, and road dust, respectively, while 2-OH-BTH and BTH showed values about an order of magnitude lower. The size distribution of most BTHs suggests that they are distributed in the finest fraction of road dust. An exception was given by 2-SCNMeS-BTH being present only in particles with a diameter > 1 mm.


Subject(s)
Dust , Environmental Monitoring , Environmental Monitoring/methods , Benzothiazoles , Particulate Matter , Water Quality
2.
J Environ Manage ; 324: 116348, 2022 Dec 15.
Article in English | MEDLINE | ID: mdl-36174466

ABSTRACT

Highway stormwater (HSW) runoff is a significant pathway for transferring microplastics from land-based sources to the other surrounding environmental compartments. Small microplastics (SMPs, 5-100 µm), additives, plasticizers, natural, and nonplastic synthetic fibers, together with other components of micro-litter (APFs), were assessed in HSW samples via Micro-FTIR; oleo-extraction and purification procedures previously developed were optimized to accomplish this goal. The distribution of SMPs and APFs observed in distinct HSW runoff varied significantly since rainfall events may play a crucial role in the concentration and distribution of these pollutants. The SMPs' abundance varied from 11932 ± 151 to 18966 ± 191 SMPs/L. The dominating polymers were vinyl ester (VE), polyamide 6 (PA6), fluorocarbon, and polyester (PES). The APFs' concentrations ranged from 12825 ± 157 to 96425 ± 430 APFs/L. Most APFs originated from vehicle and tire wear (e.g., Dioctyl adipate or 5-Methyl-1H-benzotriazole). Other sources of these pollutants might be pipes, highway signs, packaging from garbage debris, road marking paints, atmospheric deposition, and other inputs. Assessing SMPs in HSW runoff can help evaluating the potential threat they may represent to receiving water bodies and air compartments. Besides, APFs in HSW runoff may be efficient proxies of macro- and microplastic pollution.


Subject(s)
Environmental Pollutants , Water Pollutants, Chemical , Microplastics , Plastics , Plasticizers , Environmental Monitoring/methods , Water Pollutants, Chemical/analysis
3.
ACS Med Chem Lett ; 5(10): 1133-7, 2014 Oct 09.
Article in English | MEDLINE | ID: mdl-25313326

ABSTRACT

An efficient synthesis of α-amino-γ-lactone ketolide (3) was developed, which provided a versatile intermediate for the incorporation of a variety of aryl and heteroaryl groups onto the C-21 position of clarithromycin via HBTU-mediated amidation. The biological data for this important new class of macrolides revealed significantly potent activity against erythromycin-susceptible strains as well as efflux-resistant and erythromycin MLSB-resistant strains of S. pneumoniae and S. pyogenes. In addition, ketolide 11o showed excellent in vitro antibacterial activity against H. influenzae strain as compared to telithromycin. These results indicate that C-21 substituted γ-lactone ketolides have potential as a next generation macrolide antibiotics.

4.
Antibiotics (Basel) ; 3(2): 193-215, 2014 May 09.
Article in English | MEDLINE | ID: mdl-27025744

ABSTRACT

Since the 1940s ß-lactam antibiotics have been used to treat bacterial infections. However, emergence and dissemination of ß-lactam resistance has reached the point where many marketed ß-lactams no longer are clinically effective. The increasing prevalence of multidrug-resistant bacteria and the progressive withdrawal of pharmaceutical companies from antibiotic research have evoked a strong reaction from health authorities, who have implemented initiatives to encourage the discovery of new antibacterials. Despite this gloomy scenario, several novel ß-lactam antibiotics and ß-lactamase inhibitors have recently progressed into clinical trials, and many more such compounds are being investigated. Here we seek to provide highlights of recent developments relating to the discovery of novel ß-lactam antibiotics and ß-lactamase inhibitors.

5.
Molecules ; 18(10): 12264-89, 2013 Oct 08.
Article in English | MEDLINE | ID: mdl-24108395

ABSTRACT

The review reports a short biography of the Italian naturalized chemist Hugo Schiff and an outline on the synthesis and use of his most popular discovery: the imines, very well known and popular as Schiff Bases. Recent developments on their "metallo-imines" variants have been described. The applications of Schiff bases in organic synthesis as partner in Staudinger and hetero Diels-Alder reactions, as "privileged" ligands in the organometallic complexes and as biological active Schiff intermediates/targets have been reported as well.


Subject(s)
Chemistry, Organic/history , Schiff Bases/history , Animals , Antimalarials/chemical synthesis , Antiviral Agents/chemical synthesis , Chemistry Techniques, Synthetic/history , Germany , History, 19th Century , History, 20th Century , Humans , Italy , Ketones/chemistry , Organometallic Compounds/chemistry , Schiff Bases/chemistry
6.
Bioorg Med Chem ; 21(18): 5811-22, 2013 Sep 15.
Article in English | MEDLINE | ID: mdl-23910991

ABSTRACT

The enzyme α-glucosidase has attracted interest owing to its involvement in the digestive process of carbohydrate, its role in intracellular glycoprotein trafficking, tumorigenesis and viral infection. In this study, several members of a new family of N-heteroarylmethyl substituted azasugars were synthesized and evaluated as α-glucosidase inhibitors. We systematically investigated the effect of different N-substituents as well as the role of hydroxyl and carboxylate moieties on the piperidine ring. The compounds N-heteroarylmethyl-5-hydroxy-1,2,5,6-tetrahydropyridine-3-carboxylic acid emerged as potent α-glucosidase inhibitors. Unlike Acarbose and other clinically relevant α-glucosidase inhibitors, these compounds act through a reversible uncompetitive mechanism of inhibition which make them attractive candidates for drug development.


Subject(s)
Carboxylic Acids/chemistry , Drug Design , Enzyme Inhibitors/chemistry , Glycoside Hydrolase Inhibitors , Carboxylic Acids/chemical synthesis , Carboxylic Acids/metabolism , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/metabolism , Imino Sugars/chemistry , Kinetics , Protein Binding , Substrate Specificity , alpha-Glucosidases/metabolism
7.
Med Law Rev ; 21(3): 474-86, 2013.
Article in English | MEDLINE | ID: mdl-23552505

ABSTRACT

This article provides an account of the European Court on Human Rights' Second Section decision in the case Costa and Pavan v Italy. The judgment found that the Italian Statute on Assisted Reproduction (Law 40/2004), and particularly its prohibition to use in vitro fertilisation and pre-implantation genetic diagnosis (PGD) to prevent the birth of children affected by genetically transmissible conditions, breached Article 8 of the European Convention on Human Rights (ECHR). In fact, the statute in question permits only infertile people to access medically assisted reproduction techniques and forbids PGD and embryo selection. The Court regarded that the rationale of these prohibitions-identified by the Italian Government with the need to prevent eugenic practices as well as to protect the health of the unborn and of the woman-was at odds with the fact that Italian law allows pre-natal screening and therapeutic abortions in case foetal abnormalities are diagnosed. In order to clarify the decision's significance, the paper goes on to analyse the rationale of Law 40/2004 in the Italian legal and political context. Emphasis is placed on the fact that this statute is extremely controversial at domestic level, because many of its provisions-including those considered by the Strasbourg Court-are inherently contradictory and contrast with the settled constitutional principles on abortion, as many domestic authorities highlighted. In this context, should the commented decision be confirmed by the Grand Chamber, it may provide a basis to bring consistency back to the Italian regulation of assisted reproduction. Finally, the paper considers the appeal lodged by the Italian Government to the Grand Chamber, and in particular the contention that the European Court had failed to respect Italy's margin of appreciation. In this regard, it is argued that, under Law 40/2004, individuals face illogical and discriminatory restrictions to their right to private and family life and that therefore, even if an outright violation of Article 8 ECHR could not be found, there appears to be at least a breach of Article 8 in conjunction with Article 14 ECHR.


Subject(s)
Preimplantation Diagnosis , Reproductive Techniques, Assisted/legislation & jurisprudence , Abortion, Legal , Embryo Disposition , Female , Genetic Diseases, Inborn/prevention & control , Humans , Italy
8.
Bioorg Med Chem Lett ; 21(11): 3216-21, 2011 Jun 01.
Article in English | MEDLINE | ID: mdl-21549597

ABSTRACT

Several aromatic/heterocyclic sulfonamide scaffolds have been used to synthesize compounds incorporating NO-donating moieties of the nitrate ester type, which have been investigated for the inhibition of five physiologically relevant human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms: hCA I (offtarget), II, IV and XII (antiglaucoma targets) and IX (antitumor target). Some of the new compounds showed effective in vitro inhibition of the target isoforms involved in glaucoma, and the X-ray crystal structure of one of them revealed factors associated with the marked inhibitory activity. In an animal model of ocular hypertension, one of the new compounds was twice more effective than dorzolamide in reducing elevated intraocular pressure characteristic of this disease, anticipating their potential for the treatment of glaucoma.


Subject(s)
Nitric Oxide , Protein Isoforms/chemical synthesis , Sulfonamides/chemical synthesis , Animals , Carbonic Anhydrase Inhibitors/chemical synthesis , Carbonic Anhydrase Inhibitors/chemistry , Carbonic Anhydrase Inhibitors/pharmacology , Crystallography, X-Ray , Disease Models, Animal , Glaucoma/drug therapy , Humans , Models, Molecular , Molecular Structure , Nitric Oxide/chemistry , Ocular Hypertension/drug therapy , Protein Isoforms/chemistry , Protein Isoforms/pharmacology , Rabbits , Sulfonamides/chemistry , Sulfonamides/pharmacology , Sulfonamides/therapeutic use , Thiophenes/chemistry , Thiophenes/pharmacology , Thiophenes/therapeutic use
9.
Bioorg Med Chem Lett ; 19(23): 6565-70, 2009 Dec 01.
Article in English | MEDLINE | ID: mdl-19854054

ABSTRACT

Novel bi-functional compounds with a nitric oxide (NO)-releasing moiety bound to a dorzolamide scaffold were investigated. Several compounds were synthesized and their activity as selective carbonic anhydrase inhibitors (CAI) evaluated in vitro on recombinant hCA type I, II and IV enzyme isoforms where they showed different degrees of potency and selectivity to hCA II. A high resolution X-ray crystal structure for the CA II adduct with 8 confirmed the high affinity of this class of compounds for the enzyme. Compounds 4, 6, and 8 showed highly potent and efficacious NO-mediated properties as assessed by their vascular relaxant effect on methoxamine-precontracted rabbit aortic rings. Finally, compounds 4 and 6 exerted potent intraocular pressure (IOP) lowering effects in vivo in normotensive rabbits thereby anticipating their potential for the treatment of hypertensive glaucoma.


Subject(s)
Carbonic Anhydrase II/antagonists & inhibitors , Carbonic Anhydrase Inhibitors/therapeutic use , Glaucoma, Open-Angle/drug therapy , Nitric Oxide/chemistry , Sulfonamides/therapeutic use , Thiophenes/therapeutic use , Animals , Carbonic Anhydrase Inhibitors/chemical synthesis , Carbonic Anhydrase Inhibitors/chemistry , Crystallography, X-Ray , Drug Discovery , Models, Molecular , Molecular Structure , Rabbits , Structure-Activity Relationship , Sulfonamides/chemical synthesis , Sulfonamides/chemistry , Thiophenes/chemical synthesis , Thiophenes/chemistry
11.
Bioorg Med Chem Lett ; 19(10): 2785-8, 2009 May 15.
Article in English | MEDLINE | ID: mdl-19361986

ABSTRACT

A novel class of timolol derivatives with nitric oxide (NO)-donating moieties achieved chemical stability yet under physiologically relevant conditions released timolol and NO. Hindered esters A were designed and synthesized, whose 'triggered' release relied on enzymatic hydrolysis of the nitrate ester in A to B, that in turn cyclized to liberate timolol.


Subject(s)
Nitric Oxide/metabolism , Timolol/chemistry , Adrenergic beta-Antagonists/metabolism , Drug Stability , Esters/chemistry , Esters/metabolism , Guanylate Cyclase/antagonists & inhibitors , Guanylate Cyclase/metabolism
12.
J Med Chem ; 52(16): 5058-68, 2009 Aug 27.
Article in English | MEDLINE | ID: mdl-20560642

ABSTRACT

A series of (nitrooxyacyloxy)methyl esters of aspirin were synthesized and evaluated as new NO-donor aspirins. Different amounts of aspirin were released in serum from these products according to the nature of nitrooxyacyloxy moiety present. In the aromatic series, there is a rather good linear correlation between the amount of aspirin released and the potencies of the products in inhibiting platelet aggregation induced by collagen. Both the native compounds and the related nitrooxy-substituted acid metabolites were able to relax rat aorta strips precontracted with phenylephrine, in keeping with a NO-induced activation of the sGC as a mechanism that underlies the vasodilator effect. The products here described are new improved examples of NO-donor aspirins containing nitrooxy groups. They could represent an alternative to the use of aspirin in a variety of clinical applications.


Subject(s)
Aspirin/analogs & derivatives , Aspirin/chemical synthesis , Nitrates/chemical synthesis , Nitric Oxide Donors/chemical synthesis , Platelet Aggregation Inhibitors/chemical synthesis , Vasodilator Agents/chemical synthesis , Animals , Aorta/drug effects , Aorta/physiology , Aspirin/blood , Aspirin/pharmacology , Drug Stability , Esters , Humans , Hydrogen-Ion Concentration , Hydrolysis , In Vitro Techniques , Male , Muscle Contraction/drug effects , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/physiology , Nitrates/blood , Nitrates/pharmacology , Nitric Oxide Donors/blood , Nitric Oxide Donors/pharmacology , Platelet Aggregation Inhibitors/blood , Platelet Aggregation Inhibitors/pharmacology , Rats , Rats, Wistar , Structure-Activity Relationship , Vasodilator Agents/blood , Vasodilator Agents/pharmacology
13.
J Med Chem ; 51(6): 1894-903, 2008 Mar 27.
Article in English | MEDLINE | ID: mdl-18293898

ABSTRACT

A new class of products in which the phenol group of salicylic acid is linked to alkanoyl moieties bearing nitrooxy functions has been synthesized and studied for their polyvalent actions. The products were stable in acid and neutral media, while they were hydrolyzed in human serum. Their half-lives were dependent upon the structure of alkanoyl moieties. The products showed anti-inflammatory activities similar to aspirin when tested in the carrageenan-induced paw edema assay in the rat. Interestingly, unlike aspirin, they showed reduced or no gastrotoxicity in a lesion model in rats at equimolar doses. A number of them were able to inhibit platelet aggregation induced by collagen in human platelet-rich plasma. All of the products were capable of relaxing rat aortic strips precontracted with phenylephrine in a concentration-dependent manner. Selected members of this new class of nonsteroidal anti-inflammatory drugs might represent possible safer alternatives to aspirin in different clinical settings.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/chemistry , Nitric Oxide Donors/chemistry , Nitro Compounds/chemistry , Platelet Aggregation Inhibitors/chemistry , Salicylic Acid/chemistry , Vasodilator Agents/chemistry , Animals , Anti-Inflammatory Agents, Non-Steroidal/classification , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Aorta, Thoracic/drug effects , Aspirin/pharmacology , Carrageenan , Drug Evaluation, Preclinical , Edema/chemically induced , Edema/drug therapy , Humans , Hydrolysis , Male , Molecular Structure , Nitric Oxide Donors/classification , Nitric Oxide Donors/pharmacology , Platelet Aggregation/drug effects , Platelet Aggregation Inhibitors/classification , Platelet Aggregation Inhibitors/pharmacology , Rats , Rats, Wistar , Salicylic Acid/classification , Salicylic Acid/pharmacology , Solutions/chemistry , Stereoisomerism , Vasodilator Agents/classification , Vasodilator Agents/pharmacology , Water/chemistry
14.
Bioorg Med Chem Lett ; 17(18): 5265-9, 2007 Sep 15.
Article in English | MEDLINE | ID: mdl-17681467

ABSTRACT

Synthesis and antibacterial activity of a new class of ketolide antibiotics, exemplified by the prototype GW680788X (1), are described. The structure of (1) has been elucidated by spectroscopic analysis. The good antibacterial activity shown by (1) in comparison with clarithromycin prompted us to consider this compound as a lead molecule for further exploration.


Subject(s)
Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/pharmacology , Ketolides/chemical synthesis , Ketolides/pharmacology , Microbial Sensitivity Tests , Models, Molecular
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