These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Pyrrolo[2,3-h]quinolinones: a new ring system with potent photoantiproliferative activity.
    Author: Barraja P, Diana P, Montalbano A, Dattolo G, Cirrincione G, Viola G, Vedaldi D, Dall'Acqua F.
    Journal: Bioorg Med Chem; 2006 Dec 15; 14(24):8712-28. PubMed ID: 16987666.
    Abstract:
    A new class of compounds, the pyrrolo[2,3-h]quinolin-2-ones, nitrogen isosters of the angular furocoumarin Angelicin, was synthesized with the aim of obtaining new photochemotherapeutic agents with increased antiproliferative activity and lower undesired toxic effects than the lead compound. Two synthetic pathways were approached to allow the isolation both of the dihydroderivatives 10-17 and of the aromatic ring system 23. Compounds 10-17 showed a remarkable phototoxicity and a great UVA dose dependence reaching IC(50) values at submicromolar level. Intracellular localization of these compounds has been evaluated by means of fluorescence microscopy using tetramethylrhodamine methyl ester and acridine orange, which are specific fluorescent probes for mitochondria and lysosomes, respectively. A weak co-staining was observed with mitochondrial stain, whereas a specific localization in lysosomes was observed. Studies directed to elucidate the mode of action of this series of compounds revealed that they do not intercalate with DNA and do not induce photodamage to the macromolecule. On the contrary, they induce significative photodamage to lipids and proteins.
    [Abstract] [Full Text] [Related] [New Search]