Claudia Melis

Isatin: a privileged scaffold for the design of carbonic anhydrase inhibitors

Abstract The isatin scaffold is the constitutive fragment of several natural and synthetic bioactive molecules. Albeit several benzene sulphonamide-based carbonic anhydrase inhibitors (CAIs) have been reported, only recently isatin benzene sulphonamides have been studied and proposed as CAIs. In this study we have designed, synthesised, and evaluated the biological activity of a series of differently substituted isatin-based benzene sulphonamides which have been designed for the inhibition of carbonic anhydrase isoforms. The activity of all the synthesised compounds was evaluated towards human carbonic anhydrase I, II, IX, and XII isozymes. Our results indicate that the nature and position of substituents on the isatin ring can modulate both activity and isozyme selectivity.

New 4-[(3-cyclohexyl-4-aryl-2,3-dihydro-1,3-thiazol-2-ylidene)amino]benzene-1-sulfonamides, synthesis and inhibitory activity toward carbonic anhydrase I, II, IX, XII.

A series of 4-[(3-cyclohexyl-4-aryl-2,3-dihydro-1,3-thiazol-2-ylidene)amino]benzene-1-sulfonamides was synthesised and the activity of the new compounds as inhibitors of hCA I, II, IX, and XII was evaluated. These new derivatives exhibited some peculiarities with respect to previously reported sulfonamide based inhibitors of CA. We observed that the nature of the substituents in the position 3 and 4 of the dihydro-thiazole ring was relevant in determining both activity and selectivity profiles.

Isatin thiazoline hybrids as dual inhibitors of HIV-1 reverse transcriptase

Abstract A series of 3-3-{2-[2-3-methyl-4-phenyl-2,3-dihydro-1,3-thiazol-2-ylidene]hydrazin-1-ylidene-2,3-dihydro-1H-indol-2-one derivatives has been designed and synthesized to study their activity on both HIV-1 (Human Immunodeficiency Virus type 1) RT (Reverse Transcriptase) associated functions. These derivatives are analogs of previously reported series whose biological activity and mode of action have been investigated. In this work we investigated the influence of the introduction of a methyl group in the position 3 of the dihydrothiazole ring and of a chlorine atom in the position 5 of the isatin nucleus. The new synthesized compounds are active towards both DNA polymerase and ribonuclease H in the µM range. The nature of the aromatic group in the position 4 of the thiazole was relevant in determining the biological activity.

Through scaffold modification to 3,5-diaryl-4,5-dihydroisoxazoles: new potent and selective inhibitors of monoamine oxidase B

Abstract 3,5-Diaryl-4,5-dihydroisoxazoles were synthesized and evaluated as monoamine oxidase (MAO) enzyme inhibitors and iron chelators. All compounds exhibited selective inhibitory activity towards the B isoform of MAO in the nanomolar concentration range. The best performing compound was preliminarily evaluated for its ability to bind iron II and III cations, indicating that neither iron II nor iron III is coordinated. The best compounds racemic mixtures were separated and single enantiomers inhibitory activity evaluated. Furthermore, none of the synthesised compounds exhibited activity towards MAO A. Overall, these data support our hypothesis that 3,5-diaryl-4,5-dihydroisoxazoles are promising scaffolds for the design of neuroprotective agents.

N-Acylbenzenesulfonamide Dihydro-1,3,4-oxadiazole Hybrids: Seeking Selectivity toward Carbonic Anhydrase Isoforms

A series of N-acylbenzenesulfonamide dihydro-1,3,4-oxadiazole hybrids (EMAC8000a–m) was designed and synthesized with the aim to target tumor associated carbonic anhydrase (hCA) isoforms IX and XII. Most of the compounds were selective inhibitors of the tumor associated hCA XII. Moreover, resolution of EMAC8000d racemic mixture led to the isolation of the levorotatory eutomer exhibiting an increase of hCA XII inhibition potency and selectivity with respect to hCA II. Computational studies corroborated these data. Overall our data indicate that both substitution pattern and stereochemistry of dihydro-1,3,4-oxadiazole could be considered as key factors to determine activity and selectivity toward hCA isozymes. These results can provide further indication for the design and optimization of selective hCA inhibitors.

Exploring the thiazole scaffold for the identification of new agents for the treatment of fluconazole resistant Candida

Abstract Cyclohexyliden- and 2-methylcyclohexyliden-hydrazo-4-arylthiazoles were synthesized and tested as antifungal agents. All compounds exhibited minimal inhibitory concentration (MIC) values comparable with those of fluconazole (FLC). Moreover, some compounds showed fungicidal activity at low concentration. Worth noting five out of nine compounds were active towards Candida albicans 25 FLC resistant isolated from clinical specimens. The cellular toxicity was evaluated and none of the compounds is toxic at the MIC. On the basis of our data we can conclude that these derivatives are promising agents for the treatment of resistant C. albicans.

Is intangible cultural heritage able to promote sustainability in tourism

Purpose – This paper aims to focus on evaluating the rich cultural intangible heritage of Sardinia Island, and how such a heritage can contribute to the implementation of tourism during the low season. The purpose is also to verify whether the enhancement of intangible heritage attractors, could be a driver for the sustainability of the islands tourism.Design/methodology/approach – A qualitative approach is used in order to explore a multiple case study: the multifaceted expressions of the Holy Week. This is a cultural event that constitutes a part of the Christian festivity of Easter, which is characterized by traditional processions and ancient rituals widespread in various towns and cities around the island.Findings – Intangible cultural heritage provides an additional opportunity to increase the level of tourism in Sardinia Island.Research limitations/implications – This study has its limitations: it focuses only on a specific typology of event. Further studies should be taken into consideration in o...

Phenylpropenoids from Bupleurum fruticosum as Anti-Human Rhinovirus Species A Selective Capsid Binders

The dichloromethane extract of the leaves of Bupleurum fruticosum was found to inhibit the replication of human rhinovirus (HRV) serotypes 14 and 39. Bioassay-guided fractionation led to the isolation of seven phenylpropenol derivatives (3-9), two polyacetylenes (1 and 2), and one monoterpene (10). Compounds 1 and 10 were identified as previously undescribed secondary metabolites after extensive 1D and 2D NMR experiments as well as high-resolution mass spectrometry. Compounds 2, 4, and 5 showed a selective inhibition of viral replication against HRV39 serotype, with 2 and 4 being the most active, with EC50 values of 1.8 ± 0.02 and 2.4 ± 0.04 μM. Mechanism of action studies indicated that 4 behaves not only as a capsid binder, interfering with the early phases of virus replication, but also as a late-phase replication inhibitor. Docking experiments were performed to confirm the ability of the antiviral phenylpropenoids to selectively fit into the hydrophobic pocket of VP1-HRV39.

Revitalizing the Barter: The Case of Sardex.Net

“Creativity without boundaries” could be the best expression to describe the activity of an enterprise which was founded a few years ago in Sardinia (Italy). Its concept is a rediscovery of barter, the ancient practice to obtain goods from other people. The basic rules of barter rest unmodified nowadays: networked firms produce/sell goods or services and exchange them with goods and services provided by other firms in the network. Starting from the awareness that about barter firms has been written little, the goal of this article is to analyze this concept in order to show how information and communication technologies create new ways to make business. Our aim is in particular to understand, through the case study of Sardex.net, how this firm works, and how it improves thanks to the Internet the performance of the networked firms. We try moreover to find out whether and how the tourism is involved.

Exploring the Effectiveness of Web Ads Via Greenwald and Leavitt’s Involvement Model

Taking the continuous growth of online advertising into account, the necessity to adequately measure the effectiveness of web ads emerges, by having an approach broader than the Click Through Rate (CTR). As scholars underline web ads can be unconsciously processed even when not clicked on, and it is therefore necessary to consider the involvement level of the users and the elaboration level of the messages even though users do not interact with the advertisement by clicking on it. This paper presents a preliminary effort to verify the effectiveness of web advertisements using the involvement model elaborated by Greenwald and Leavitt, basing it on the analysis of how users interact with ads and the way in which they process the information contained in them. To pursue this goal we conducted a survey using an online questionnaire sent via e-mail to the Economics students at the University of Cagliari.