New Furan Side Tetracyclic Allopsoralen Derivatives: Synthesis and Photobiological Evaluation.
From: Department of Pharmaceutical Sciences, University of Padova, Via Marzolo 5, 35131 Padova, Italy. lisa.dallavia@unipd.it
Journal of medicinal chemistry
- Publish Date: Jul 2006
- ISSN: 0022-2623
- Volume: 49
- Issue: 14
- Pages: 4317-26
- Medium: Print
- Language: English
- Citation (JAMA): Dalla Via Lisa, Mammi Stefano, Uriarte Eugenio, et al. New Furan Side Tetracyclic Allopsoralen Derivatives: Synthesis and Photobiological Evaluation.. J. Med. Chem. Jul 2006;49:4317-26
Abstract
Novel tetracyclic allopsoralen derivatives characterized by the condensation of a fourth cyclohexenylic (5-7) or benzenic (8-10) ring at the furan side and a methoxy (5 and 8), a hydroxy (6 and 9), or a dimethylaminopropoxy (7 and 10) side chain in the 10 position of the chromophore were prepared. Compounds 7 and 10 showed a strong photoantiproliferative activity, up to 3 orders of magnitude higher than that of the photochemotherapeutic drug 8-methoxypsoralen (8-MOP). The investigation into the mechanism of action demonstrated for 10 the capacity to intercalate between DNA base pairs in the ground state, to give rise to a covalent photoaddition upon UVA irradiation, and to inhibit polymerase chain reaction (PCR) in a sequence-specific manner. Conversely, compound 7 showed a limited capacity to form an intercalative complex and the lack of ability to photoadd to the macromolecule, thus revealing a novel and unusual behavior for an allopsoralen derivative.
Mesh Headings (Keywords): Animals, Antineoplastic Agents, Cell Line, Tumor, DNA Adducts, DNA Topoisomerases, Type II, Darkness, Drug Screening Assays, Antitumor, Furans, Guinea Pigs, Heterocyclic Compounds with 4 or More Rings, Humans, Intercalating Agents, PUVA Therapy, Polymerase Chain Reaction, Psoralens, Skin, Structure-Activity Relationship, Thymine, Toxicity Tests, Ultraviolet Rays
Check for Full Text / PubMed Unique Identifier (PMID): 16821791
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