5 results on '"Domenico Iacopetta"'
Search Results
2. Inhibition of Human Topoisomerase II byN,N,N-Trimethylethanammonium Iodide Alkylcarbazole Derivatives
- Author
-
Marco Ponassi, Jessica Ceramella, Giuseppe Rosace, Maria Grazia Bonomo, Maria Stefania Sinicropi, Pasquale Longo, Noemi Muià, Domenico Iacopetta, Carmela Saturnino, Anna Caruso, Annaluisa Mariconda, and Camillo Rosano
- Subjects
0301 basic medicine ,medicine.medical_treatment ,Iodide ,N-alkylcarbazoles ,apoptosis ,caspases ,docking simulations ,topoisomerase II ,01 natural sciences ,Biochemistry ,Drug Discovery ,Topoisomerase II Inhibitors ,Ellipticines ,General Pharmacology, Toxicology and Pharmaceutics ,Caspase ,chemistry.chemical_classification ,biology ,Chemistry ,Alkaloid ,Metastatic breast cancer ,Molecular Docking Simulation ,Molecular Medicine ,Female ,Toxicology and Pharmaceutics (all) ,Carbazoles ,Antineoplastic Agents ,Breast Neoplasms ,Structure-Activity Relationship ,03 medical and health sciences ,Pharmacology ,Drug Discovery3003 Pharmaceutical Science ,Pharmacology, Toxicology and Pharmaceutics (all) ,Organic Chemistry ,Breast cancer ,Cell Line, Tumor ,medicine ,Humans ,Cell Proliferation ,Chemotherapy ,010405 organic chemistry ,Topoisomerase ,Settore CHIM/07 - Fondamenti Chimici delle Tecnologie ,medicine.disease ,0104 chemical sciences ,Quaternary Ammonium Compounds ,DNA Topoisomerases, Type II ,030104 developmental biology ,Apoptosis ,Cancer research ,biology.protein ,Drug Screening Assays, Antitumor - Abstract
Chemotherapy is used for the treatment of all stages of breast cancer, including the metastatic stage of the disease. Treatment regimens are generally tailored for each patient's particular situation. However, chemotherapeutic agents are the leading cause of serious drug-related adverse effects; moreover, drug resistance often occurs. In this study, we designed and synthesized a new series of N-alkylcarbazoles derived from ellipticine, an alkaloid with a carbazole skeleton initially used in the treatment of metastatic breast cancer and later dismissed because of poor aqueous solubility and severe side effects. After evaluating the binding modes of our class of newly synthesized compounds with human topoisomerase II (hTopo II), we performed hTopo II decatenation assays, identifying compound 4 f (2-(4-((3-chloro-9H-carbazol-9-yl)pentyl)piperazin-1-yl)-N,N,N-trimethylethanammonium iodide) as a good inhibitor. Moreover, 4 f and 4 g (2-(4-((3-chloro-9H-carbazol-9-yl)hexyl)piperazin-1-yl)-N,N,N-trimethylethanammonium iodide) showed a good anti-proliferative activity toward breast cancer cells, causing apoptosis by activation of the caspase pathway. Interestingly, the activity of these two compounds on triple-negative MDA-MB-231 cells, which tend to be highly metastatic and aggressive, is strictly connected to the observed inhibition of hTopo II.
- Published
- 2018
3. Old Drug Scaffold, New Activity: Thalidomide-Correlated Compounds Exert Different Effects on Breast Cancer Cell Growth and Progression
- Author
-
Alessia Catalano, Maria Stefania Sinicropi, Jessica Ceramella, Maria Cristina Caroleo, Giovanni Lentini, Alessia Carocci, Domenico Iacopetta, and Rosita Curcio
- Subjects
Vascular Endothelial Growth Factor A ,0301 basic medicine ,Epithelial-Mesenchymal Transition ,Angiogenesis ,Apoptosis ,Breast Neoplasms ,Pharmacology ,medicine.disease_cause ,Biochemistry ,03 medical and health sciences ,chemistry.chemical_compound ,Cell Movement ,Cell Line, Tumor ,Drug Discovery ,medicine ,Humans ,Vimentin ,General Pharmacology, Toxicology and Pharmaceutics ,Cell Proliferation ,Tumor Necrosis Factor-alpha ,business.industry ,Organic Chemistry ,Cancer ,Cadherins ,medicine.disease ,Thalidomide ,Vascular endothelial growth factor ,030104 developmental biology ,Microscopy, Fluorescence ,chemistry ,Tumor progression ,Cancer cell ,MCF-7 Cells ,Molecular Medicine ,Female ,Tumor necrosis factor alpha ,Carcinogenesis ,business ,medicine.drug - Abstract
Thalidomide was first used for relief of morning sickness in pregnant women and then withdrawn from the market because of its dramatic effects on normal fetal development. Over the last decades, it has been used successfully for the treatment of several pathologies, including cancer. Many analogues with improved activity have been synthesized and tested. Herein we report some effects on the growth and progression of MCF-7 and MDA-MB-231 breast cancer cells by a small series of thalidomide-correlated compounds, which are very effective at inducing cancer cell death by triggering TNFα-mediated apoptosis. The most active compounds are able to drastically reduce the migration of breast cancer cells by regulation of the two major proteins involved in epithelial-mesenchymal transition (EMT): vimentin and E-cadherin. Moreover, these compounds diminish the intracellular biosynthesis of vascular endothelial growth factor (VEGF), which is primarily involved in the promotion of angiogenesis, sustaining tumor progression. The multiple features of these compounds that act on various key points of the tumorigenesis process make them good candidates for preclinical studies.
- Published
- 2017
4. The biochemical properties of the mitochondrial thiamine pyrophosphate carrier from Drosophila melanogaster
- Author
-
Antonella Santoro, Domenico Iacopetta, Vincenza Dolce, Loredana Capobianco, Adele Chimento, Ferdinando Palmieri, Giuseppina De Filippis, Anna Rita Cappello, Rosita Curcio, Valeria Mariajolanda Calcagnile, Angelo Vozza, and Chiara Carrisi
- Subjects
chemistry.chemical_classification ,Cell Biology ,Mitochondrion ,Biology ,Mitochondrial carrier ,Biochemistry ,Pyrophosphate ,Cofactor ,Transport protein ,chemistry.chemical_compound ,chemistry ,biology.protein ,Nucleotide ,Inner mitochondrial membrane ,Molecular Biology ,Thiamine pyrophosphate - Abstract
The mitochondrial carriers are a family of transport proteins that shuttle metabolites, nucleotides and cofactors across the inner mitochondrial membrane. The genome of Drosophila melanogaster encodes at least 46 members of this family. Only five of these have been characterized, whereas the transport functions of the remainder cannot be assessed with certainty. In the present study, we report the functional identification of two D. melanogaster genes distantly related to the human and yeast thiamine pyrophosphate carrier (TPC) genes as well as the corresponding expression pattern throughout development. Furthermore, the functional characterization of the D. melanogaster mitochondrial thiamine pyrophosphate carrier protein (DmTpc1p) is described. DmTpc1p was over-expressed in bacteria, the purified protein was reconstituted into liposomes, and its transport properties and kinetic parameters were characterized. Reconstituted DmTpc1p transports thiamine pyrophosphate and, to a lesser extent, pyrophosphate, ADP, ATP and other nucleotides. The expression of DmTpc1p in Saccharomyces cerevisiaeTPC1 null mutant abolishes the growth defect on fermentable carbon sources. The main role of DmTpc1p is to import thiamine pyrophosphate into mitochondria by exchange with intramitochondrial ATP and/or ADP.
- Published
- 2010
5. A fourth ADP/ATP carrier isoform in man: identification, bacterial expression, functional characterization and tissue distribution
- Author
-
Pasquale Scarcia, Ferdinando Palmieri, Vincenza Dolce, and Domenico Iacopetta
- Subjects
Gene isoform ,Mitochondrial carrier ,Isoform ,Subfamily ,Antiporter ,Molecular Sequence Data ,Biophysics ,Transport ,Mitochondrion ,Biology ,Polymerase Chain Reaction ,Biochemistry ,Structural Biology ,Genetics ,Humans ,Protein Isoforms ,Amino Acid Sequence ,Molecular Biology ,Sequence Homology, Amino Acid ,Cell Biology ,biochemical phenomena, metabolism, and nutrition ,bacterial infections and mycoses ,Transport protein ,Liver ,Liposomes ,ADP/ATP carrier ,bacteria ,ATP–ADP translocase ,Heterologous expression ,Mitochondrial ADP, ATP Translocases ,Plasmids - Abstract
The mitochondrial ADP/ATP carriers (AACs) catalyze the exchange of cytosolic ADP for matrix ATP. We have identified and characterized a novel member of the AAC subfamily of mitochondrial metabolite transport proteins, termed AAC4. The AAC4 gene maps to human chromosome 4q28.1, and its product AAC4 is 66–68% identical to human AAC 1–3 and is localized to mitochondria. AAC4 transcripts are exclusively present in liver, testis and brain unlike those of AAC 1–3. Consistent with its belonging to the AAC subfamily, upon heterologous expression and reconstitution into liposomes AAC4 exchanges ADP for ATP by an electrogenic antiport mechanism with high specificity and high sensitivity to carboxyatractyloside and bongkrekic acid.
- Published
- 2004
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.