A new scaffold of topoisomerase I inhibitors: Design, synthesis and biological evaluation.
The synthesis of a new hexacyclic system was realized starting from tryptamines and exploiting as a key step a sequential Pd-catalyzed N-arylation/acylation reaction. Having topoisomerases as biological target and the campthotecins class as benchmark, the new scaffold was decorated with substituents having different polarity and tested as Topoisomerase I inhibitors.
DISFARM, Sezione di Chimica Organica "A. Marchesini", Università di Milano, Via Venezian 21, 20133, Milano, Italy.
Alberto
A
Mazza
DISFARM, Sezione di Chimica Organica "A. Marchesini", Università di Milano, Via Venezian 21, 20133, Milano, Italy. Electronic address: egle.beccalli@unimi.it.
Egle M
EM
Beccalli
DISFARM, Sezione di Chimica Organica "A. Marchesini", Università di Milano, Via Venezian 21, 20133, Milano, Italy.
Alessandro
A
Contini
Fondazione per la Biologia e la Medicina della Rigenerazione T.E.S.-Tissue Engineering and Signalling Onlus, Via F. Marzolo 13, 35131, Padova, Italy.
Aida Nelly
AN
Garcia-Argaez
Dipartimento di Scienze del farmaco, Università di Padova, Via F. Marzolo 5, 35131, Padova, Italy.
Lisa
L
Dalla Via
DISFARM, Sezione di Chimica Organica "A. Marchesini", Università di Milano, Via Venezian 21, 20133, Milano, Italy.
Maria Luisa
ML
Gelmi
D000215:Acylation; D000586:Amination; D002384:Catalysis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D004247:DNA / Q000378:metabolism; D004264:DNA Topoisomerases, Type I / Q000737:chemistry / Q000378:metabolism*; D015195:Drug Design; D006801:Humans; D010165:Palladium / Q000737:chemistry; D011487:Protein Conformation; D059004:Topoisomerase I Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D014363:Tryptamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
D059004:Topoisomerase I Inhibitors; D014363:Tryptamines; D010165:Palladium; D004247:DNA; D004264:DNA Topoisomerases, Type I
Amination; Pd-catalysis; Polyheterocyclic systems; Pyrroloacridines; Topoisomerase inhibitors; Triptamine