A5043864360- Phenothiazines and Benzothiazines Synthesis and Activities
- Synthesis and Biological Evaluation
- HIV/AIDS drug development and treatment
- HIV Research and Treatment
- Cancer therapeutics and mechanisms
- Synthesis and biological activity
- Computational Drug Discovery Methods
- Antibiotic Resistance in Bacteria
- Quinazolinone synthesis and applications
- Antibiotics Pharmacokinetics and Efficacy
- Hepatitis C virus research
- Mosquito-borne diseases and control
- Antimicrobial Resistance in Staphylococcus
- Structural and Chemical Analysis of Organic and Inorganic Compounds
- Influenza Virus Research Studies
- Tuberculosis Research and Epidemiology
- Melanoma and MAPK Pathways
- RNA and protein synthesis mechanisms
- Bioactive Compounds and Antitumor Agents
- Synthesis and Characterization of Heterocyclic Compounds
- Cytomegalovirus and herpesvirus research
- Monoclonal and Polyclonal Antibodies Research
- Analytical Chemistry and Chromatography
- Viral Infections and Immunology Research
- Synthesis and Reactivity of Sulfur-Containing Compounds
University of Perugia
2015-2024
University of Naples Federico II
2015
Rega Institute for Medical Research
2004-2009
University of Padua
1996-2009
Istituto di Genetica Molecolare
2009
Novel (United States)
2009
Biological E (India)
2009
KU Leuven
2004-2008
Centre National de la Recherche Scientifique
2006
Molecular Discovery (United Kingdom)
2004
The emergence of multidrug resistant HIV-1 strains and the inability HAART to eradicate virus from infected patients demand new drugs able interfere with an alternative step replicative cycle. naphthyridone 3 (HM13N), described in present study, is a promising anti-HIV agent due its ability inhibit Tat-mediated transcription potent antiviral activity observed acutely, chronically, latently cells. absence any tendency select for resistance mutations vitro adds potential clinical value this...
Overexpression of efflux pumps is an important mechanism by which bacteria evade the effects substrate antimicrobial agents. Inhibition such a promising strategy to circumvent this resistance mechanism. NorA Staphylococcus aureus pump that confers reduced susceptibility many structurally unrelated agents, including fluoroquinolones, resulting in multidrug resistant phenotype. In work, series 2-phenyl-4(1H)-quinolone and 2-phenyl-4-hydroxyquinoline derivatives, obtained modifying flavone...
The increasing resistance to antibacterials commonly employed in the clinic and growth of multidrug resistant strains suggest that development new therapeutic approaches should be primary concern. In this context, EPIs may restore life old drugs. present work, EPI activity COX-2 inhibitor celecoxib was confirmed a class pyrazolo[4,3-c][1,2]benzothiazine 5,5-dioxide analogues acting as inhibitors Staphylococcus aureus NorA efflux pump identified.
In continuing our efforts to identify small molecules able disrupt the interaction of polymerase acidic protein–basic protein 1 (PA–PB1) subunits influenza virus (Flu) RNA-dependent RNA polymerase, this paper is devoted optimization a dihydrotriazolopyrimidine derivative, previously identified through structure-based drug discovery. The structure modifications performed around bicyclic core led identification compounds endowed with both ability PA–PB1 and anti-Flu activity no cytotoxicity....
RNA dependent polymerases (RdRp) are essential enzymes for flavivirus replication. Starting from an in silico docking analysis we identified a pyridobenzothiazole compound, HeE1-2Tyr, able to inhibit West Nile and Dengue RdRps activity vitro, which proved effective against different flaviviruses cell culture. Crystallographic data show that HeE1-2Tyr binds between the fingers domain priming loop of virus RdRp (Site 1). Conversely, enzyme kinetics, binding studies mutational analyses suggest...
Indoleamine 2,3-dioxygenase 1 (IDO1) catalyzes the first step in kynurenine pathway of tryptophan (Trp) degradation that produces several biologically active Trp metabolites. L-kynurenine (Kyn), byproduct by IDO1, promotes immunoregulatory effects via activation Aryl hydrocarbon Receptor (AhR) dendritic cells (DCs) and T lymphocytes. We here identified nuclear coactivator 7 (NCOA7) as a molecular target 3-hydroxyanthranilic acid (3-HAA), metabolite produced downstream Kyn along pathway. In...
Small molecules that specifically target viral polymerases—crucial enzymes governing genome transcription and replication—play a pivotal role in combating infections. Presently, approved polymerase inhibitors cover nine human viruses, spanning both DNA RNA viruses. This review provides comprehensive analysis of these licensed drugs, encompassing nucleoside/nucleotide (NIs), non-nucleoside (NNIs), mutagenic agents. For each compound, we describe the specific targeted virus related enzyme,...
A series of 6-aminoquinolone compounds were evaluated for their in vitro activity against human immunodeficiency virus type 1 (HIV-1). Compound 12a, bearing a methyl substituent at the N-1 position and 4-(2-pyridyl)-1-piperazine moiety C-7 position, was most active inhibiting HIV-1 replication on de novo infected C8166 lymphoblastoid cell lines. The 12a EC50 value 0.1 μM, 7−20-fold lower concentration relative to that 8a 7a containing cyclopropyl tert-butyl respectively. When C-6 amino group...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTQuinolonecarboxylic acids. 2. Synthesis and antibacterial evaluation of 7-oxo-2,3 dihydro-7H-pyrido[1,2,3-de][1,4]benzothiazine-6-carboxylic acidsVioletta Cecchetti, Arnaldo Fravolini, Renata Fringuelli, Giuseppe Mascellani, Piergiuseppe Pagella, Maurizio Palmioli, Giorgio Segre, Patrizia TerniCite this: J. Med. Chem. 1987, 30, 3, 465–473Publication Date (Print):March 1, 1987Publication History Published online1 May 2002Published inissue 1 March...
Overexpression of efflux pumps is an important mechanism by which bacteria evade the effects antimicrobial agents that are substrates. NorA a Staphylococcus aureus pump confers reduced susceptibility to many structurally unrelated agents, including fluoroquinolones, biocides, and dyes, resulting in multidrug resistant (MDR) phenotype. In this work, series 2-phenylquinoline derivatives was designed means ligand-based pharmacophore modeling attempt identify improved S. inhibitors (EPIs). Most...
An intriguing opportunity to address antimicrobial resistance is represented by the inhibition of efflux pumps. Focusing on NorA, most important pump Staphylococcus aureus, an inhibitors (EPIs) library was used for ligand-based pharmacophore modeling studies. By exploitation obtained models, in silico drug repositioning approach allowed identification novel and potent NorA EPIs.
Antimicrobial resistance (AMR) represents a hot topic in drug discovery. Besides the identification of new antibiotics, use nonantibiotic molecules to block mechanisms is powerful alternative. Bacterial efflux pumps exert an early step AMR development by allowing bacteria grow at subinhibitorial concentrations. Thus, pump inhibitors (EPIs) offer great opportunity fight AMR. Given our experience developing Staphylococcus aureus NorA EPIs, this work, starting from 2-phenylquinoline hit 1, we...
ABSTRACT There have been several reports that convulsions, although rare, occur in patients who receive fluoroquinolones. In this study, the proconvulsant effects exhibited by a novel series of 6-desfluoroquinolones and some classic quinolones on pentylenetetrazole (PTZ)-induced seizures mice were evaluated compared. Animals intraperitoneally injected with vehicle or quinolone derivatives (5 to 100 μg/g body weight) 30 min before subcutaneous (s.c.) administration PTZ (40 μg/g). each...
In this study we report the design, synthesis, and activity against bovine viral diarrhea virus (BVDV) of a novel series acridone derivatives. BVDV is responsible for major losses in cattle. The also considered to be valuable surrogate hepatitis C (HCV) antiviral drug studies. Some synthesized acridones elicited selective anti-BVDV with EC50 values ranging from 0.4 4 μg/mL were not cytotoxic at concentrations that 25- 200-fold higher (CC50 >100 μg/mL). It was proven most potent derivative 10...
The limited number of drug classes licensed for treatment influenza virus (Flu), together with the continuous emergence viral variants and resistant mutants, highlights urgent need to find antivirals novel mechanisms action. In this context, RNA-dependent RNA polymerase (RdRP) subunits assembly has emerged as an attractive target. Starting from a cycloheptathiophene-3-carboxamide derivative recently identified by us its ability disrupt interaction between PA PB1 RdRP, we have designed...
Treatment of dengue virus (DENV) and other flavivirus infections is an unmet medical need. The highly conserved flaviviral NS5 RNA-dependent RNA polymerase (RdRp) attractive antiviral target that interacts with NS3 viral within the replication complex assembly. Biochemical cell-based evidence indicate targeting cavity B may lead to dual RdRp NS5–NS3 interaction inhibitors. By ligand-based design around 1H-pyrido[2,1-b][1,3]benzothiazol-1-one (PBTZ) 1, we identified new potent selective DENV...
On the basis of our recent findings that 6-aminoquinolones inhibit HIV Tat-mediated transactivation, we have designed a broad series derivatives identifying novel potent agents such as 6-desfluoroquinolones 24 (HM12) and 27 (HM13), which showed pronounced anti-HIV activity in acutely, chronically, latently HIV-1 infected cell cultures. We demonstrate here highly molecules can be obtained by optimizing substituent various positions quinolone nucleus.
We report the synthesis and structure−activity relationship (SAR) of a large series acridones acridone-fragment derivatives designed on basis selective antihepatitis C virus (HCV) activity shown by acridone 2, previously studied as potential antibovine viral diarrhea (BVDV) compound. The evaluation their ability to inhibit HCV replication in Huh-5-2 cells led identification new, inhibitors. This indicates that skeleton, when properly functionalized, is suitable scaffold obtain anti-HCV...
We have previously reported that the 6-aminoquinolone chemotype is a privileged scaffold to obtain antibacterial and antiviral agents. Herein we describe design, synthesis, enzymatic cellular characterization of new derivatives as potent inhibitors NS5B polymerase, an attractive viable therapeutic target develop safe anti-HCV The 6-amino-7-[4-(2-pyridinyl)-1-piperazinyl]quinolone derivative 8 proved be best compound this series, exhibiting IC50 value 0.069 μM against polymerase selective...
The NS5B RNA-dependent RNA polymerase is an attractive target for the development of novel and selective inhibitors hepatitis C virus replication. To identify structural hits as anti-HCV agents, we performed structure-based virtual screening our in-house library followed by rational drug design, organic synthesis, biological testing. These studies led to identification pyrazolobenzothiazine scaffold a suitable template obtaining agents targeting polymerase. best compound this series was...