Novel pyrone side tetracyclic psoralen derivatives: synthesis and photobiological evaluation.

Basic Information

ID: ALA1145066

Journal: J Med Chem

Title: Novel pyrone side tetracyclic psoralen derivatives: synthesis and photobiological evaluation.

Authors: Dalla Via L, Uriarte E, Quezada E, Dolmella A, Ferlin MG, Gia O.

Abstract: This study reports the synthesis of tetrahydrobenzo- (4-6) and benzopsoralen (7-9) derivatives obtained by condensing the fourth ring to the pyrone side of the tricyclic psoralen moiety. The new compounds are characterized by having a methoxy, a hydroxy, or a dimethylaminopropoxy side chain inserted at position 8 of the psoralen chromophore. The evaluation of the photoantiproliferative activity on human tumor cell lines along with skin phototoxicity on guinea pigs revealed an interesting photobiological pattern for the dimethylaminopropoxy derivatives 6 and 9: they are in fact able to exert an antiproliferative effect up to 1 order of magnitude higher than that of the well-known drug 8-MOP, but they are devoid of skin phototoxicity. The ability of both 6 and 9 to photoadd to DNA is demonstrated by the isolation and characterization of the 4',5'-monoadducts. AM1 calculations were also performed to gain further insight into the molecular basis of their photobiological behavior.

CiteXplore: 12930143

DOI: 10.1021/jm0210919

Patent ID: