A5033627987- Cholinesterase and Neurodegenerative Diseases
- Computational Drug Discovery Methods
- Synthesis and Biological Evaluation
- HIV/AIDS drug development and treatment
- Antifungal resistance and susceptibility
- Synthesis and biological activity
- HIV Research and Treatment
- Trypanosoma species research and implications
- Research on Leishmaniasis Studies
- Biochemical and Molecular Research
- Synthesis and Reactivity of Heterocycles
- Pesticide Exposure and Toxicity
- Essential Oils and Antimicrobial Activity
- Fungal Infections and Studies
- Chemical Synthesis and Analysis
- Catalytic C–H Functionalization Methods
- Radical Photochemical Reactions
- Asymmetric Hydrogenation and Catalysis
- Neuroscience and Neuropharmacology Research
- Cancer therapeutics and mechanisms
- Tuberculosis Research and Epidemiology
- Plant-Microbe Interactions and Immunity
- Natural product bioactivities and synthesis
- Phenothiazines and Benzothiazines Synthesis and Activities
- Enzyme function and inhibition
Sapienza University of Rome
2016-2025
Istituto Pasteur
2015-2024
Istituto di Farmacologia Traslazionale
2018
The development of HIV-1 dual inhibitors is a highly innovative approach aimed at reducing drug toxic side effects as well therapeutic costs. integrase (IN) and reverse transcriptase-associated ribonuclease H (RNase H) are both selective targets for chemotherapy, the identification IN/RNase an attractive strategy new development. We newly synthesized pyrrolyl derivatives that exhibited good potency against IN moderate inhibition RNase function RT, confirming possibility developing obtaining...
The study presented here aimed at identifying a new class of compounds acting against Leishmania parasites, the causative agent Leishmaniasis. For this purpose, thioether derivatives our in-house library have been evaluated in whole-cell screening assays order to determine their vitro activity protozoan. Among them, promising results achieved with compound RDS 777 (6-(sec-butoxy)-2-((3-chlorophenyl)thio)pyrimidin-4-amine) (IC50 = 29.43 µM), which is able impair mechanism parasite defence...
A series of antiviral basic quinolinonyl diketo acid derivatives were developed as inhibitors HIV-1 IN. Compounds 12d,f,i inhibited IN with IC50 values below 100 nM for strand transfer and showed a 2 order magnitude selectivity over 3′-processing. These selective also RNase H low micromolar potencies. Molecular modeling studies based on both the catalytic core domains provided new structural insights future development these compounds dual inhibitors.
Cannabis oils, namely concentrated cannabis extracts, are getting plenty of attention because their therapeutic potential for treatment patients with cancer, HIV, multiple sclerosis and several other pathologies. Here we propose the use ultrasound-assisted extraction (UAE) microwave-assisted (MAE) as alternative methods to current protocols followed by pharmacists, only authorized manipulate standardized Cannabis. A third method, consisting Tween 20 surfactant, was considered. Our best...
The increasing efficiency of HAART has helped to transform HIV/AIDS into a chronic disease. Still, resistance and drug–drug interactions warrant the development new anti-HIV agents. We previously discovered hit 6, active against HIV-1 replication targeting RNase H in vitro. Because its diketo-acid moiety, we speculated that this chemotype could serve develop dual inhibitors both integrase. Here, describe series 1-benzyl-pyrrolyl diketohexenoic derivatives, 7a–y 8a–y, synthesized following...
Bifunctional quinolinonyl DKA derivatives were first described as nonselective inhibitors of 3'-processing (3'-P) and strand transfer (ST) functions HIV-1 integrase (IN), while 7-aminosubstituted proven IN (INSTIs) that also displayed activity against ribonuclease H (RNase H). In this study, we describe the design, synthesis, biological evaluation new diketo acid (DKA) characterized by variously substituted alkylating groups on nitrogen atom quinolinone ring. Removal second branch...
The resinous exudate produced by Commiphora myrrha (Nees) Engl. is commonly known as true myrrh and has been used since antiquity for several medicinal applications. Hundreds of metabolites have identified in the volatile component so far, mainly sesquiterpenes. Although efforts devoted to identifying these sesquiterpenes, phytochemical analyses performed gas-chromatography/mass spectrometry (GC–MS) where high temperature employed can promote degradation components. In this work, we report...
Background: Anticancer drug resistance is a challenging phenomenon of growing concern which arises from alteration in targets. Despite the fast speed new chemotherapeutic agent design, increasing prevalence this requires further research and treatment development. Recently, we reported aminopyrimidine compound—namely RDS 344—as potential innovative anticancer agent. Methods: Herein, report synthesis, anti-proliferative activity derivatives structurally related to 3442 obtained by carrying...
We discovered novel and selective sulfonamides/amides acting as inhibitors of the α-carbonic anhydrase (CA, EC 4.2.1.1) from pathogenic bacterium Vibrio cholerae (VchCA). This Gram-negative is causative agent cholera colonises upper small intestine where sodium bicarbonate present at a high concentration. The secondary sulfonamides amides investigated here were potent, low nanomolar VchCA whereas their inhibition human cytosolic isoforms CA I II was in micromolar range or higher. molecules...
Several (thiazol-2-yl)hydrazone derivatives from 2-, 3- and 4-acetylpyridine were synthesized tested against human monoamine oxidase (hMAO) A B enzymes. Most of them had an inhibitory effect in the low micromolar/high nanomolar range, being selective hMAO-B inhibitors also at concentrations. The structure–activity relationship, as confirmed by molecular modeling studies, proved that pyridine ring linked to hydrazonic nitrogen substituted aryl moiety C4 thiazole conferred effects on hMAO...
Heparanase is the sole mammalian enzyme capable of cleaving glycosaminoglycan heparan sulfate side chains proteoglycans. Its altered activity intimately associated with tumor growth, angiogenesis, and metastasis. Thus, its implication in cancer progression makes it an attractive target anticancer therapy. Herein, we describe design, synthesis, biological evaluation new benzazoles as heparanase inhibitors. Most designed derivatives were active at micromolar or submicromolar concentration,...
We have designed and synthesized a series of new imidazole-based compounds structurally related to an antiprotozoal agent with nanomolar activity which we identified recently. The analogues possess micromolar activities against Trypanosoma brucei rhodesiense Leishmania donovani potency Plasmodium falciparum. Most the displayed IC50 within low range cruzi, very high selectivity toward parasite. Discussion structure–activity relationships in vitro biological data for are provided number...
Due to the biological liability of diketo acid (DKA) chain, we transferred this element our previously reported anti-HIV-1 pyrrolyl derivatives a non-DKA scaffold, obtaining series pyrrolyl–pyrazole carboxylic acids as new RNase H inhibitors. Among newly synthesized derivatives, oxyphenylpyrrolyl–pyrazoles demonstrated inhibitory activities within low micromolar/submicromolar range with compound 11b being most potent. Interestingly, all tested compounds showed up 2 orders magnitude...
A new series of pyrimidine and pyridine diamines was designed as dual binding site inhibitors cholinesterases (ChEs), characterized by two small aromatic moieties separated a diaminoalkyl flexible linker. Many compounds are mixed or uncompetitive acetylcholinesterase (AChE) and/or butyrylcholinesterase (BChE) nanomolar inhibitors, with compound 9 being the most active on Electrophorus electricus AChE (EeAChE) (Ki = 0.312 μM) 22 equine BChE (eqBChE) 0.099 μM). Molecular docking molecular...
It has been more than four years since the first report of SARS-CoV-2, and humankind experienced a pandemic with an unprecedented impact. Moreover, new variants have made situation even worse. Among viral enzymes, SARS-CoV-2 main protease (Mpro) deemed promising drug target vs. COVID-19. Indeed, Mpro is pivotal enzyme for replication, it highly conserved within coronaviruses. showed high extent conservation residues essential to enzymatic activity, emphasizing its potential as develop...
To evaluate the efficacy of two nitrofuran derivatives against biofilms formed by strains Histoplasma capsulatum and to study toxicity these compounds in alternative models: Caenorhabditis elegans, Galleria mellonella, zebrafish. The metabolic activity was measured after treatment using XTT reduction assay. Scanning electron microscopy (SEM) confocal were used observe damage mature biofilms. Survival curves generated for G. while percentage survival determined C. elegans showed early at...