Synthesis and biological evaluation of new camptothecin derivatives obtained by modification of position 20.
The preparation and biological evaluation of a novel series of dimeric camptothecin derivatives are described. All the new compounds showed a significant ability to inhibit human tumor cell growth with IC(50) values ranging from 0.03 to 12.2 μM. The interference with the activity of the nuclear enzymes topoisomerases has been demonstrated, highlighting the poison effect of one of the obtained byproducts toward topoisomerase I. A moderate antiangiogenic activity has been demonstrated for one of the obtained compounds. Moreover, the effects of four new compounds on caspases activity and ROS generation have been studied on transgenic mouse cell.
Dipartimento di Chimica Organica e Industriale, Università degli Studi di Milano, Via Venezian 21, 20133 Milano, Italy.
Elena
E
Riva
Daniela
D
Comi
Stella
S
Borrelli
Francesco
F
Colombo
Bruno
B
Danieli
Jurgen
J
Borlak
Lasse
L
Evensen
James B
JB
Lorens
Gabriele
G
Fontana
Ornella Maria
OM
Gia
Lisa Dalla
LD
Via
Daniele
D
Passarella
D020533:Angiogenesis Inhibitors; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D002166:Camptothecin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D020169:Caspases / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004264:DNA Topoisomerases, Type I / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D017382:Reactive Oxygen Species; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D059004:Topoisomerase I Inhibitors; D020169:Caspases; D004264:DNA Topoisomerases, Type I; D002166:Camptothecin