Synthesis and biological activity of isoxazolidinyl polycyclic aromatic hydrocarbons: potential DNA intercalators.
Isoxazolidinyl polycyclic aromatic hydrocarbons (isoxazolidinyl-PAHs) have been synthesized in good yields by 1,3-dipolar cycloaddition methodology promoted by microwave irradiation. The structures of the obtained cycloadducts have been determined by NOE experiments and supported by computational studies at the AM1 level. The cytotoxicity and antiviral activity of the synthesized compounds have been investigated. In particular, compounds 7c and 7e show high levels of cytotoxicity on MOLT-3 leukemia cells; 7e exerts a remarkable enhancing activity on apoptosis caused by anti-fas antibody addition. Furthermore, compounds 7b and 8b exhibit specific antiviral effects against the Punta Toro virus.
Rescifina
Antonio
A
Dipartimento di Scienze Chimiche, Università di Catania, Catania 95125, Italy. arescifina@unict.it
Chiacchio
Maria A
MA
Corsaro
Antonino
A
De Clercq
Erik
E
Iannazzo
Daniela
D
Mastino
Antonio
A
Piperno
Anna
A
Romeo
Giovanni
G
Romeo
Roberto
R
Valveri
Vincenza
V
D000818:Animals; D000873:Anthracenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D004247:DNA / Q000737:chemistry; D004267:DNA Viruses / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007364:Intercalating Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007555:Isoxazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010616:Phenanthrenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011084:Polycyclic Aromatic Hydrocarbons / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011721:Pyrenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D012328:RNA Viruses / Q000187:drug effects; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014709:Vero Cells; D019014:fas Receptor / Q000502:physiology
D000873:Anthracenes; D000970:Antineoplastic Agents; D000998:Antiviral Agents; D007364:Intercalating Agents; D007555:Isoxazoles; D010616:Phenanthrenes; D011084:Polycyclic Aromatic Hydrocarbons; D011721:Pyrenes; D019014:fas Receptor; D004247:DNA; C427203:calf thymus DNA