A5067040645- Synthesis and biological activity
- Cancer therapeutics and mechanisms
- Synthesis and Biological Evaluation
- Bioactive Compounds and Antitumor Agents
- Synthesis and Reactivity of Heterocycles
- Antimicrobial Peptides and Activities
- Click Chemistry and Applications
- Synthesis and Characterization of Heterocyclic Compounds
- Synthesis and Reactions of Organic Compounds
- Bacterial biofilms and quorum sensing
- Marine Sponges and Natural Products
- Chemical Reaction Mechanisms
- Occupational and environmental lung diseases
- Synthesis and pharmacology of benzodiazepine derivatives
- Antibiotic Resistance in Bacteria
- Pancreatic and Hepatic Oncology Research
- Cancer Mechanisms and Therapy
- Phenothiazines and Benzothiazines Synthesis and Activities
- Phytochemical compounds biological activities
- Synthesis of heterocyclic compounds
- Biochemical and Molecular Research
- Quinazolinone synthesis and applications
- RNA Interference and Gene Delivery
- Synthesis and Biological Activity
- Natural product bioactivities and synthesis
University of Palermo
2015-2024
Amsterdam UMC Location Vrije Universiteit Amsterdam
2020
There is urgent need for new therapeutic strategies to fight the global threat of antibiotic resistance. The focus this Perspective on chemical agents that target most common mechanisms resistance such as enzymatic inactivation antibiotics, changes in cell permeability, and induction/activation efflux pumps. Here we assess current landscape challenges treatment at both bacterial community levels. We also discuss potential clinical application inhibitors add-on treatments serious...
Infectious diseases caused by antimicrobial-resistant strains have become a serious threat to global health, with high social and economic impact. Multi-resistant bacteria exhibit various mechanisms at both the cellular microbial community levels. Among different strategies proposed fight antibiotic resistance, we reckon that inhibition of bacterial adhesion host surfaces represents one most valid approaches, since it hampers virulence without affecting cell viability. Many structures...
Pyruvate dehydrogenase kinases (PDKs) are serine/threonine kinases, that directly involved in altered cancer cell metabolism, resulting aggressiveness and resistance. Dichloroacetic acid (DCA) is the first PDK inhibitor has entered phase II clinical; however, several side effects associated with weak anticancer activity excessive drug dose (100 mg/kg) have led to its limitation clinical application. Building upon a molecular hybridization approach, small library of 3-amino-1,2,4-triazine...
A new series of nortopsentin analogs, in which the central imidazole ring natural lead was replaced by a 1,3,4-oxadiazole or 1,3,4-thiadiazole moiety, efficiently synthesized. The antiproliferative activity all synthesized derivatives evaluated against five pancreatic ductal adenocarcinoma (PDAC) cell lines, primary culture and gemcitabine-resistant variant. more potent compounds elicited EC50 values submicromolar-micromolar range, associated with significant reduction migration. Moreover,...
Pancreatic ductal adenocarcinoma (PDAC) is one of the main aggressive types cancer, characterized by late prognosis and drug resistance. Among factors sustaining PDAC progression, alteration cell metabolism has emerged to have a key role in proliferation, invasion, resistance standard chemotherapeutic agents. Taking into account all these urgency evaluating novel options treat PDAC, present work we reported synthesis new series indolyl-7-azaindolyl triazine compounds inspired marine...
In this study, we describe the synthesis of new nortopsentin analogues, 1H-pyrrolo[2,3-b]pyridine derivatives and their biological effects in experimental models diffuse malignant peritoneal mesothelioma (DMPM), a rare rapidly fatal disease, poorly responsive to conventional therapies. The three most active compounds, 1f (3-[2-(5-fluoro-1-methyl-1H-indol-3-yl)-1,3-thiazol-4-yl]-1H-pyrrolo[2,3-b]pyridine), 3f (3-[2-(1H-indol-3-yl)-1,3-thiazol-4-yl]-1-methyl-1H-pyrrolo[2,3-b]pyridine), 1l...
2,5-bis(3′-Indolyl)pyrroles, analogues of the marine alkaloid nortopsentin, were conveniently prepared through a three step procedure in good overall yields. Derivatives 1a and 1b exhibited concentration-dependent antitumor activity towards panel 42 human tumor cell lines with mean IC50 values 1.54 μM 0.67 μM, respectively. Investigating xenografts an ex-vivo clonogenic assay revealed selective activity, whereas sensitive models scattered among various histotypes.
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...
A new series of imidazo[2,1-b][1,3,4]thiadiazole derivatives was efficiently synthesized and screened for their in vitro antiproliferative activity on a panel pancreatic ductal adenocarcinoma (PDAC) cells, including SUIT-2, Capan-1 Panc-1. Compounds 9c 9l, showed relevant all three pre-clinical models with half maximal inhibitory concentration (IC50) ranging from 5.11 to 10.8 µM, while the compounds 9e 9n were active at least one cell line. In addition, compound significantly inhibited...
New thiazole nortopsentin analogs in which one of the two indole units was replaced by a naphthyl and/or 7-azaindolyl portion, were conveniently synthesized. Among these, three derivatives showed good antiproliferative activity, particular against MCF7 cell line, with GI50 values micromolar range. Their cytotoxic effect on cells further investigated order to elucidate their mode action. Results that compounds act as pro-apoptotic agents inducing clear shift viable towards early apoptosis,...
Two new series of nortopsentin analogues, in which the imidazole ring natural product was replaced by thiazole and indole units were both substituted 7-azaindole moieties or one unit a 6-azaindole portion, efficiently synthesized. Compounds belonging to inhibited growth HCT-116 colorectal cancer cells at low micromolar concentrations, whereas they did not affect viability normal-like intestinal cells. A compound former induced apoptosis, evident as externalization plasma membrane...
Derivatives of new ring systems 11H-pyrido[3',2':4,5]pyrrolo[3,2-c]cinnoline and pyrido[3',2':4,5]pyrrolo[1,2-c][1,2,3]benzotriazine have been prepared from the key intermediates 2-(1H-pyrrolo[2,3-b]pyridin-2-yl)anilines in excellent yields (94-99%) screened by National Cancer Institute (Bethesda, MD) on about 60 human tumor cell lines derived nine cancer types. The tested compounds exhibited antiproliferative activity against all lines, showing comparable MG_MID (mean graph midpoint) values...