Synthesis and photobiological properties of 3-acylangelicins, 3-alkoxycarbonylangelicins and related derivatives.
Convenient synthesis of 3-acyl-2H-furo[2,3-h]-1-benzopyran-2-ones, esters of 2-oxo-2H-furo[2,3-h]-1-benzopyran-3-carboxylic acid and 2H-furo[2,3-h]-1-benzopyran-3-carboxamides was accomplished via aromatization of the adducts obtained by a reaction between (E)-5-dimethyl-aminomethylene-6,7-dihydrobenzofuran-4(5H)-one and the appropriate acylacetate or dialkyl malonate. These compounds are angelicin derivatives which were prepared with the aim of obtaining intrinsically monofunctional drugs for photochemotherapy, with only one photoreactive site in their molecule. The new angelicins appear to be free of the known phototoxicity of furocoumarins on the skin and at a genetic level. The 3-carboxylic esters showed significant antiproliferative activity in Ehrlich ascites cells and T2 bacteriophage; the other derivatives were only slightly effective. The features of these compounds are such that they represent a new model for non-toxic agents for photochemotherapy.
Iester
M
M
Istituto di Scienze Farmaceutiche, Università di Genova, Italy.
Fossa
P
P
Menozzi
G
G
Mosti
L
L
Baccichetti
F
F
Marzano
C
C
Simonato
M
M
D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D011564:Furocoumarins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006168:Guinea Pigs; D009153:Mutagens / Q000633:toxicity; D010100:Oxygen / Q000737:chemistry; D010777:Photochemistry; D017319:Photosensitizing Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D026082:Singlet Oxygen; D013604:T-Phages / Q000187:drug effects; D014466:Ultraviolet Rays
D004273:DNA, Neoplasm; D011564:Furocoumarins; D009153:Mutagens; D017319:Photosensitizing Agents; D026082:Singlet Oxygen; D010100:Oxygen