A5035315552- Pharmacological Receptor Mechanisms and Effects
- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Drug Transport and Resistance Mechanisms
- Cancer therapeutics and mechanisms
- Neurotransmitter Receptor Influence on Behavior
- N-Heterocyclic Carbenes in Organic and Inorganic Chemistry
- HIV/AIDS drug development and treatment
- Axial and Atropisomeric Chirality Synthesis
- Phenothiazines and Benzothiazines Synthesis and Activities
- Neuroscience and Neuropharmacology Research
- Nicotinic Acetylcholine Receptors Study
- Pharmacological Effects and Toxicity Studies
- Computational Drug Discovery Methods
- Adenosine and Purinergic Signaling
- Autism Spectrum Disorder Research
- Chemical Synthesis and Analysis
- Synthesis of β-Lactam Compounds
- S100 Proteins and Annexins
- Radiopharmaceutical Chemistry and Applications
- Synthesis and Reactivity of Heterocycles
- Cyclopropane Reaction Mechanisms
- Asymmetric Synthesis and Catalysis
- Inflammatory mediators and NSAID effects
- Synthesis of heterocyclic compounds
University of Bari Aldo Moro
2016-2025
Istituto di Farmacologia Traslazionale
2015-2017
sigma Ligands have recently been shown to cytotoxic activity, induce ceramide-dependent/caspase-independent apoptosis, and down-regulate P-glycoprotein (P-gp) mRNA levels in some mouse human models. In this study, we verified whether a mixed sigma(2) agonist/sigma(1) antagonist, PB28, was able antitumor activity enhance anthracycline efficacy two breast cancer cell lines, MCF7 ADR, both characterized by significant receptor expression, high low sigma(1) P-gp respectively. PB28 showed...
Abstract With the aim of contributing to development novel antitumor agents, high‐affinity σ 2 receptor agonists were developed, with 6,7‐dimethoxy‐2‐[4‐[1‐(4‐fluorophenyl)‐1 H ‐indol‐3‐yl]butyl]‐1,2,3,4‐tetrahydroisoquinoline ( 15 ) and 9‐[4‐(6,7‐dimethoxy‐1,2,3,4‐tetrahydroisoquinolin‐2‐yl)butyl]‐9 ‐carbazole 25 showing exceptional selectivity for subtype. Most compounds displayed notable antiproliferative activity in human MCF7 breast adenocarcinoma cells, similar corresponding...
Selenium (Se) is an essential micronutrient, recognized for its role in cellular redox systems and therapeutic potential cancer treatment. Organic selenium compounds, particularly selenocystine (SeCys), have demonstrated anticancer efficacy due to the ability induce apoptosis enhance effects of chemotherapy agents. Recent studies shown that SeCys exhibits selective toxicity against cells while sparing normal cells. Unfortunately, clinical application limited by stability solubility concerns....
1-Cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine 1 (PB28) represents an excellent lead candidate for therapeutic and/or diagnostic applications in oncology. However, because its utility is limited by relatively high degree of lipophilicity, novel analogues with reduced lipophilic character were designed substituting methylene groups more polar functional the propylene linker and at tetralin C4 position. For chiral analogues, separate enantiomers exhibited...
A series of N-(1,2,3,4-tetrahydronaphthalen-1-yl)-4-aryl-1-piperazinealkylamides was prepared and their affinity for serotonin (5-hydroxytryptamine, 5-HT) 5-HT7, 5-HT(1A), 5-HT(2A) receptors measured by in vitro binding assays. In relation to 5-HT7 receptor affinity, studies indicated that (i) the optimal alkyl chain length five methylenes, (ii) an unsubstituted 1,2,3,4-tetrahydronaphthalenyl nucleus preferred, (iii) substitution pattern aryl ring linked piperazine played a crucial role....
A series of furoxan derivatives were studied for their ability to interact with P-gp and MRP1 transporters in MDCK cells overexpressing these proteins. 3-Phenylsulfonyl substituted furoxans emerged as the most interesting compounds. All them capable inhibiting P-gp, a few also MRP1. Substituents at 4-position 3-phenylsulfonylfuroxan scaffold able modulate selectivity intensity inhibition. In some cases, they reverted inhibitor activity, namely, potentiating dependent efflux. When compounds...
Abstract The 2‐aryloxazole and 2‐arylthiazole scaffolds were used for generating compounds that we characterized their inhibitory activity toward ATP binding cassette transporters involved in multi‐drug resistance, such as BCRP MRP1, by using tumor cell lines overexpressing each transporter. These SAR studies are a significant step improving the potency against P‐glycoprotein, BCRP, MRP1. magnified image 2‐Aryloxazole derivatives evaluated P‐glycoprotein (P‐gp) well selectivity other ABC...
Despite considerable efforts by scientific research, pancreatic cancer is the fourth leading cause of related mortalities. Sigma-2 receptors, which are overexpressed in several tumors, represent promising targets for triggering selective cells death. We selected five differently structured high-affinity sigma-2 ligands (PB28, PB183, PB221, F281 and PB282) to study how they affect viability diverse (human cell lines BxPC3, AsPC1, Mia PaCa-2, Panc1 mouse Panc-02, KCKO KP-02) this reflected...
Previous studies showed that some lamellarin-resembling annelated azaheterocyclic carbaldehydes and related imino adducts, sharing the 1-phenyl-5,6-dihydropyrrolo[2,1-a]isoquinoline (1-Ph-DHPIQ) scaffold, are cytotoxic in tumor cells may reverse multidrug resistance (MDR) mediated by P-glycoprotein (P-gp). Herein, we synthesized evaluated for their antiproliferative activity four cell lines (RD, HCT116, HeLa, A549) ability of inhibiting P-gp-mediated MDR ten diversely substituted 1-Ph-DHPIQ...
Starting from the high affinity σ2 receptor ligand 2, (PB28), we synthesized amino derivative 4 and coupled it to an NHS-ester activated sepharose stationary phase column elute a crude protein prepared by lysed human SK-N-SH neuroblastoma cells. We characterized SDS−PAGE gel electrophoresis stained bands MALDI-MS LC-MS-MS analysis. The MASCOT MS-MS ion search program led identification of components. six eluted proteins had molecular weight ranging 13 kDa 26 were histone proteins. A 40S...
To find Δ8−Δ7 sterol isomerase (EBP) selective ligands, various arylpiperazines previously studied and structurally related to some σ receptors ligands were preliminarily screened. Consequently, a novel series of 2- or 2,6-disubstituted (CH3, CH3O, Cl, F) cis- trans-4-(4-aryl)cyclohexyl-1-(2-pyridyl)piperazines was developed. Radioreceptor binding assays evidenced cis-19, cis-30 cis-33 as new with nanomolar affinity toward EBP site good selectivity relative EBP-related receptors. The most...