0000000000038576

AUTHOR

Michele De Franco

showing 5 related works from this author

New tricyclic systems as photosensitizers towards triple negative breast cancer cells.

2022

AbstractNineteen pyrrolo[1,2-h][1,7]naphthyridinones and pyrido[2,3-c]pyrrolo[1,2-a]azepinones were synthesized as new tricyclic systems in which the pyridine ring is annelated to the 6,7-dihydroindolizin-8(5H)-one and 5,6,7,8-tetrahydro-9H-pyrrole[1,2-a]azepine-9-one moieties to obtain potential photosensitizing agents. They were tested for their photoantiproliferative activity on a triple-negative breast cancer cell line, MDA-MB-231, in the dark and under UVA light (2.0 J/cm2). We demonstrated that their toxicity, only when exposed to light, was primarily due to the generation of reactive oxygen species while their photodegradation products were not responsible for their activity. The mos…

7]naphthyridinonePhotosensitizing AgentsPyrrolo[12-h][17]naphthyridinoneCell DeathMDA-MB-231Organic ChemistryPhototoxic activityTriple Negative Breast NeoplasmsApoptosisPyrido[23-c]pyrrolo[12-a]azepinoneTriple-negative breast cancerPyrrolo[1Drug DiscoveryMolecular MedicineHumans2-h][1Pyrido[23-c]pyrrolo[12-a]azepinoneMDA-MB-231; Photosensitizing agents; Phototoxic activity; Pyrido[23-c]pyrrolo[12-a]azepinone; Pyrrolo[12-h][17]naphthyridinone; Triple-negative breast cancerReactive Oxygen SpeciesArchives of pharmacal research
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1,2,4-Amino-triazine derivatives as pyruvate dehydrogenase kinase inhibitors: Synthesis and pharmacological evaluation

2023

: Among the different hallmarks of cancer, deregulation of cellular metabolism turned out to be an essential mechanism in promoting cancer resistance and progression. The pyruvate dehydrogenase kinases (PDKs) are well known as key regulators in cells metabolic process and their activity was found to be overexpressed in different metabolic alerted types of cancer, including the high aggressive pancreatic ductal adenocarcinoma (PDAC). To date few PDK inhibitors have been reported, and the different molecules developed are characterized by structural chemical diversity. In an attempt to find novel classes of potential PDK inhibitors, the molecular hybridization approach, which combine two or m…

PharmacologyPDK inhibitors4-Amino-triazines1Organic ChemistryDrug Discovery2124-Amino-triazinesGeneral MedicineKRAS-mutated pancreatic cancerLigand-based homology modelingSettore CHIM/08 - Chimica Farmaceutica124-Amino-triazines; KRAS-mutated pancreatic cancer; Ligand-based homology modeling; PDK inhibitorsEuropean Journal of Medicinal Chemistry
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Insight on pyrimido[5,4-g]indolizine and pyrimido[4,5-c]pyrrolo[1,2-a]azepine systems as promising photosensitizers on malignant cells

2022

Searching for new small molecules as photosensitizing agents, we have developed a class of twenty-five pyrimido[5,4-g]indolizine and pyrimido[4,5-c]pyrrolo[1,2-a]azepines with a good substitution pattern defining a versatile synthetic pathway to approach the title ring system. All compounds were evaluated for their photocytotoxicity on a triple negative human breast cancer cell line (MDA-MB-231) in the dark and under UVA light (2.0 J/cm2). The most effective compounds exhibited a photoantiproliferative activity with IC50 values up to nanomolar ranges. Interestingly, these new developed compounds showed high selectivity towards cancerous cells with respect to non-cancerous ones. Moreover, fo…

PharmacologyMDA-MB-231Triple negative human breast cancerOrganic ChemistryPhototoxic activityIndolizinesAntineoplastic AgentsApoptosisTriple Negative Breast Neoplasms4-g]indolizinespyrimido[4General MedicineAzepinespyrimido[54-g]indolizinespyrimido[45-c]pyrrolo[12-a]azepinesTriple negative human breast cancerMDA-MB-231Photosensitizing agentsPhototoxic activitypyrimido[5Photosensitizing agents5-c]pyrrolo[1pyrimido[45-c]pyrrolo[12-a]azepinesCell Line Tumor2-a]azepinesTriple negative human breast cancerMDA-MB-231Photosensitizing agentsPhototoxic activityDrug DiscoveryHumanspyrimido[54-g]indolizines
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Discovery of the 3-Amino-1,2,4-triazine-Based Library as Selective PDK1 Inhibitors with Therapeutic Potential in Highly Aggressive Pancreatic Ductal …

2023

Pyruvate dehydrogenase kinases (PDKs) are serine/threonine kinases, that are directly involved in altered cancer cell metabolism, resulting in cancer aggressiveness and resistance. Dichloroacetic acid (DCA) is the first PDK inhibitor that has entered phase II clinical; however, several side effects associated with weak anticancer activity and excessive drug dose (100 mg/kg) have led to its limitation in clinical application. Building upon a molecular hybridization approach, a small library of 3-amino-1,2,4-triazine derivatives has been designed, synthesized, and characterized for their PDK inhibitory activity using in silico, in vitro, and in vivo assays. Biochemical screenings showed that …

PDK inhibitorsOrganic ChemistryKras-mutated pancreatic ductal adenocarcinomaGeneral Medicine3-amino-124-triazine derivativesantitumor agentsCatalysisbis-indole derivativesComputer Science ApplicationsInorganic Chemistryligand-based homology modelingPhysical and Theoretical ChemistryMolecular BiologySpectroscopyInternational Journal of Molecular Sciences
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Structural Manipulations of Marine Natural Products Inspire a New Library of 3-Amino-1,2,4-Triazine PDK Inhibitors Endowed with Antitumor Activity in…

2023

Pancreatic ductal adenocarcinoma (PDAC) is one of the main aggressive types of cancer, characterized by late prognosis and drug resistance. Among the main factors sustaining PDAC progression, the alteration of cell metabolism has emerged to have a key role in PDAC cell proliferation, invasion, and resistance to standard chemotherapeutic agents. Taking into account all these factors and the urgency in evaluating novel options to treat PDAC, in the present work we reported the synthesis of a new series of indolyl-7-azaindolyl triazine compounds inspired by marine bis-indolyl alkaloids. We first assessed the ability of the new triazine compounds to inhibit the enzymatic activity of pyruvate de…

nortopsentin analoguespancreatic ductal adenocarcinoma (PDAC); nortopsentin analogues; antitumor activity; pyruvate dehydrogenase kinases (PDKs); cytotoxic activity; metabolic alterations; ligand-based homology modeling; KRASDrug Discoveryligand-based homology modelingKRASPharmaceutical Scienceantitumor activitymetabolic alterationspancreatic ductal adenocarcinoma (PDAC)Pharmacology Toxicology and Pharmaceutics (miscellaneous)cytotoxic activitypyruvate dehydrogenase kinases (PDKs)
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