A5054053277- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- Influenza Virus Research Studies
- Phenothiazines and Benzothiazines Synthesis and Activities
- Antibiotic Resistance in Bacteria
- RNA and protein synthesis mechanisms
- Antimicrobial Resistance in Staphylococcus
- Quinazolinone synthesis and applications
- Computational Drug Discovery Methods
- Tuberculosis Research and Epidemiology
- Mosquito-borne diseases and control
- Toxin Mechanisms and Immunotoxins
- Cancer therapeutics and mechanisms
- PARP inhibition in cancer therapy
- DNA and Nucleic Acid Chemistry
- Synthesis and Biological Evaluation
- Click Chemistry and Applications
- Pneumocystis jirovecii pneumonia detection and treatment
- Cytomegalovirus and herpesvirus research
- Antibiotics Pharmacokinetics and Efficacy
- interferon and immune responses
- Synthesis and biological activity
- Cervical Cancer and HPV Research
- Monoclonal and Polyclonal Antibodies Research
- Traumatic Ocular and Foreign Body Injuries
University of Perugia
2016-2025
Istituto di Farmacologia Traslazionale
2010
Policlinico Umberto I
2009
Sapienza University of Rome
2009
Istituto di Genetica Molecolare
2009
University of Padua
2009
Rega Institute for Medical Research
2008-2009
Novel (United States)
2009
Biological E (India)
2009
KU Leuven
2008
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...
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....
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...
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...
We report [1,2,4]triazolo[3,4-b]benzothiazole (TBT) as a new inhibitor scaffold, which competes with nicotinamide in the binding pocket of human poly- and mono-ADP-ribosylating enzymes. The mode was studied through analogues cocrystal structures TNKS2, PARP2, PARP14, PARP15. Based on substitution pattern, we were able to identify 3-amino derivatives 21 (OUL243) 27 (OUL232) inhibitors mono-ARTs PARP7, PARP10, PARP11, PARP12, PARP15 at nM potencies, being most potent PARP10 described date...
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...
Dengue virus (DENV) serotypes 1–4 are mosquito‐borne flaviviruses that responsible for significant morbidity and mortality worldwide, particularly in tropical subtropical regions. Although two vaccines have been approved, their unbalanced efficacy across poses potential risks specific populations. There currently no approved antiviral treatments DENV, resulting a clear medical need, especially endemic countries. In this study, medicinal chemistry optimization of the pyridobenzothiazolone...
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...
Two facile and efficient one-step procedures for the regioselective synthesis of 7-aryl-5-methyl- 5-aryl-7-methyl-2-amino-[1,2,4]triazolo[1,5-a]pyrimidines have been developed, via reactions 3,5-diamino-1,2,4-triazole with variously substituted 1-aryl-1,3-butanediones 1-aryl-2-buten-1-ones, respectively. The excellent yield and/or regioselectivity shown by decreased when ethyl 5-amino-1,2,4-triazole-3-carboxylate was used. [1,2,4]Triazolo[1,5-a]pyrimidine being a privileged scaffold, herein...
Expanded CAG trinucleotide repeats in Huntington's disease (HD) are causative for neurotoxicity. The mutant repeat RNA encodes neurotoxic polyglutamine proteins and can lead to a toxic gain of function by aberrantly recruiting RNA-binding proteins. One these is the MID1 protein, which induces aberrant Huntingtin (HTT) protein translation upon binding. Here we have identified set binder candidates silico methods. those, furamidine, reduces level binding HTT mRNA other target vitro....
The thiopyranopyridine moiety was synthesized as a new heterocyclic base to be inserted at the C-7 position of selected quinolone nuclei followed by determination antibacterial activity against strains Staphylococcus aureus. Selected thiopyranopyridinylquinolones showed significant antimicrobial activity, including having mutations in gyrA and grlA well other overexpressing NorA multidrug (MDR) efflux pump. Most derivatives did not appear substrates. effect thiopyranopyridinyl substituent on...
Abstract The activity of the cyclin‐dependent kinase 9 (CDK9) is critical for HIV‐1 Tat‐mediated transcription and represents a promising target antiviral therapy. Here we present computational studies that, along with preliminary synthetic efforts, allowed us to identify characterize new class nontoxic anti‐CDK9 chemotypes based on 2‐phenylquinazolinone scaffold. Inhibition CDK9 translated into ability interfere selectively transactivation viral promoter in inhibition reactivation from...