A5050213616- Synthesis and biological activity
- Ion Channels and Receptors
- Metabolomics and Mass Spectrometry Studies
- Computational Drug Discovery Methods
- Chemical Synthesis and Analysis
- SARS-CoV-2 and COVID-19 Research
- Phytochemicals and Antioxidant Activities
- Antimicrobial Peptides and Activities
- Bioactive Compounds and Antitumor Agents
- Influenza Virus Research Studies
- Neuroscience and Neuropharmacology Research
- Click Chemistry and Applications
- Ion channel regulation and function
- Machine Learning in Bioinformatics
- Cancer, Hypoxia, and Metabolism
- Mass Spectrometry Techniques and Applications
- Cardiac electrophysiology and arrhythmias
- Sirtuins and Resveratrol in Medicine
- Cancer therapeutics and mechanisms
- Free Radicals and Antioxidants
- Cancer-related Molecular Pathways
- Toxin Mechanisms and Immunotoxins
- Endoplasmic Reticulum Stress and Disease
- Liver Disease Diagnosis and Treatment
- Biochemical and Structural Characterization
University of Salerno
2013-2025
European Biomedical Research Institute of Salerno
2019-2022
University of Naples Federico II
2016-2018
University of Messina
2013-2015
In this paper we present the design, synthesis, and biological evaluation of a new series peptidomimetics acting as potent anti-SARS-CoV-2 agents. Starting from our previously described Main Protease (M
Analogues of the previously described spiro[imidazo[1,5-c]thiazole-3,3'-indoline]-2',5,7(6H,7aH)-trione p53 modulators were prepared to explore new structural requirements at thiazolidine domain for antiproliferative activity and modulation. In cell, was evaluated against two human tumor cell lines. Derivative 5-bromo-3'-(cyclohexane carbonyl)-1-methyl-2-oxospiro[indoline-3,2'-thiazolidine] (4n) emerged as most potent compound this series, inhibiting in vitro 30% p53-MDM2 interaction 5 μM...
New analogs of nortopsentin, a natural 2,4-bis(3′-indolyl)imidazole alkaloid, in which the central imidazole ring lead was replaced by 1,2,4-oxadiazole moiety, and 7-azaindole portion substituted original indole were efficiently synthesized. Among all derivatives, prescreened against HCT-116 colon rectal carcinoma cell line, two most active compounds selected further investigated different human tumor cells showing IC50 values micromolar submicromolar range. Flow cytometric analysis...
Here, we report the design of new analogues spirooxoindolepyrrolidine nucleus as modulators p53 activity. Compounds (3R,7aR)-6-(4-chlorobenzyl)-1H-spiro[imidazo[1,5-c]thiazole-3,3'-indoline]-2',5,7(6H,7aH)-trione (9c) and (3R,7aR)-5'-methyl-6-(3,4,5-trimethoxybenzyl)-1H-spiro[imidazo[1,5-c]thiazole-3,3'-indoline]-2',5,7(6H,7aH)-trione (10d) are most potent compounds this series, inhibiting cell growth different human tumor cells at submicromolar micromolar concentrations, respectively....
Abstract A new series of topsentin analogs, in which the central imidazole ring natural lead was replaced by a 1,2,4‐oxadiazole moiety, efficiently synthesized. All derivatives were pre‐screened for antiproliferative activity against National Cancer Institute (NCI‐60) cell lines panel. The five most potent compounds further investigated various pancreatic ductal adenocarcinoma (PDAC) lines, including SUIT‐2, Capan‐1, and Panc‐1 cells, eliciting EC 50 values micromolar sub‐micromolar range,...
Neuronal Kv7 channels represent important pharmacological targets for hyperexcitability disorders including epilepsy. Retigabine is the prototype activator clinically approved seizure treatment; however, severe side effects associated with long-term use have led to its market discontinuation. Building upon recently described cryoEM structure of Kv7.2 complexed retigabine and on previous structure–activity relationship studies, a small library analogues has been designed, synthesized,...
Pharmacological modulation of the transient receptor potential melastatin type 8 (TRPM8) is currently under investigation as a new approach for treatment pain and other diseases. In this study, series N-substituted tryptamines was prepared to explore structural requirements determining TRPM8 modulation. Using fluorescence-based screening assay, we identified two compounds acting an activator (2-(1H-indol-3-yl)-N-(4-phenoxybenzyl)ethanamine, 21) or inhibitor...
TRPM8 has been implicated in nociception and pain is currently regarded as an attractive target for the pharmacological treatment of neuropathic syndromes. A series analogues N, N'-dibenzyl tryptamine 1, a potent antagonist, was prepared screened using fluorescence-based vitro assay based on menthol-evoked calcium influx stably transfected HEK293 cells. The tryptophan derivative 14 identified (IC50 0.2 ± nM) selective antagonist. In vivo, showed significant coverage both icilin-induced WDS...
The cannabinoid system is one of the most investigated neuromodulatory systems because its involvement in multiple pathologies such as cancer, inflammation, and psychiatric diseases. Recently, CB2 receptor has gained increased attention considering crucial role modulating neuroinflammation several pathological conditions like neurodegenerative Here we describe rational design pyrrole-based analogues, which led to a potent pharmacokinetically suitable full agonist particularly effective...
The most severe outcome of COVID-19 infection is the development interstitial pneumonia causing acute lung injury (ALI) and/or respiratory distress syndrome (ARDS), both responsible for infected patients' mortality. ALI and ARDS are characterized by a leakage plasma components into lungs, compromising their ability to expand optimally engage in gas exchange with blood, resulting failure. We have previously reported that zonulin, protein dictating epithelial endothelial permeability several...
The design of multitarget drugs represents a promising strategy in medicinal chemistry and seems particularly suitable for the discovery anti-inflammatory drugs. Here, we describe identification an indoline-based compound inhibiting both 5-lipoxygenase (5-LOX) soluble epoxide hydrolase (sEH). In silico analysis in-house library identified nine compounds as potential 5-LOX inhibitors. Enzymatic cellular assays revealed indoline derivative 43 notable inhibitor, guiding new analogues. These...
Salivary gland tumors are relatively uncommon neoplasms that represent less than 5% of head and neck tumors, about 90% in the parotid gland. The wide variety histologies tumor characteristics makes diagnosis treatment challenging. In present study, Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) was used to discriminate pathological regions patient-derived biopsies by metabolomic lipidomic profiles. Fresh frozen tissues were analyzed MALDI time-of-flight...
Abstract Background Early diagnosis of hepatocellular carcinoma (HCC) is essential towards the improvement prognosis and patient survival. Circulating markers such as α-fetoprotein (AFP) micro-RNAs represent useful tools but still have limitations. Identifying new can be fundamental to improve both prognosis. In this approach, we harness potential metabolomics lipidomics uncover signatures HCC. Methods A combined untargeted plasma profiling 102 HCV-positive patients was performed by HILIC...
ROR1 kinase is an underexplored promising target for the development of novel anticancer drugs, being strongly expressed in several cancer cell lines, but poorly non‐tumor cells. This property, together with scarce number molecules effective against ROR1, led us to design and develop a research program aimed discovery new chemical entities able inhibit thus interfering its pro‐tumoral activity. Step‐by‐step silico studies guided synthesis para‐phenylenediamine‐based compounds. SPR CETSA...
Kv7 K+ channels represent attractive pharmacological targets for the treatment of different neurological disorders, including epilepsy. In this paper, 42 conformationally restricted analogues prototypical activator retigabine have been synthesized and tested by electrophysiological patch-clamp experiments as agonists. When compared to (0.93 ± 0.43 μM), EC50s Kv7.2 current enhancements compound 23a (0.08 0.04 μM) were lower, whereas no change in potency was observed 24a (0.63 0.07 μM)....
Transient receptor potential melastatin 8 (TRPM8) ion channel represents a valuable pharmacological option for several therapeutic areas. Here, series of conformationally restricted derivatives the previously described TRPM8 antagonist N,N′-dibenzyl tryptophan 4 were prepared and characterized in vitro by Ca2+-imaging patch-clamp electrophysiology assays. Molecular modeling studies led to identification broad well-defined interaction network these inside binding site, underlying their...