Methyltrioxorhenium catalysed synthesis of highly oxidised aryltetralin lignans with anti-topoisomerase II and apoptogenic activities.
A novel and efficient procedure to prepare highly oxidised aryltetralin lignans, such as isopodophyllotoxone and (-)-aristologone derivatives, by oxidation of podophyllotoxin and galbulin with methylrhenium trioxide (MTO) and novel MTO heterogeneous catalysts is reported. It is noteworthy that in the case of isopodophyllotoxone derivatives the functionalisation of the C-4 position of the C-ring and the ring-opening of the D-lactone moiety increased the activity against topoisomerase II while causing the undesired inhibition of tubulin polymerisation to disappear. The novel (-)-aristologone derivatives showed apoptogenic activity against resistant human lymphoma cell lines.
Saladino
Raffaele
R
INFM, della Tuscia, via S.Camillo De Lellis, I-01100 Viterbo, Italy. saladino@unitus.it
Fiani
Cinzia
C
Belfiore
Maria Cristina
MC
Gualandi
Giampiero
G
Penna
Sabrina
S
Mosesso
Pasquale
P
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002384:Catalysis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D017705:Lignans / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry*; D010084:Oxidation-Reduction; D011034:Podophyllotoxin / Q000737:chemistry / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000737:chemistry*; D059005:Topoisomerase II Inhibitors
D004791:Enzyme Inhibitors; D017705:Lignans; D009942:Organometallic Compounds; D013764:Tetrahydronaphthalenes; D059005:Topoisomerase II Inhibitors; C411866:methyltrioxorhenium VII; D004250:DNA Topoisomerases, Type II; D011034:Podophyllotoxin