N-deacetyl-N-aminoacylthiocolchicine derivatives: synthesis and biological evaluation on MDR-positive and MDR-negative human cancer cell lines.
A new series of N-deacetyl-N-(N-trifluoroacetylaminoacyl)thiocolchicine derivatives 9-15 have been synthesized starting from the corresponding N-deacetylthiocolchicine (3) and the N-trifluoroacetylamino acids 5-8 which were used as a racemic mixture. The trifluoroacetyl protecting group has been removed easily, giving the corresponding N-deacetyl-N-aminoacylthiocolchicines 16-22. Optical pure compounds 9-22 were isolated from the diastereoisomeric mixture or were prepared starting from compound 3 and an optical pure amino acid derivative; the configuration of each compound was assigned unequivocally. The diastereoisomeric couples of amino acids synthesized were tested, and their antiproliferative activity on MDR-positive and MDR-negative human cancer cell lines was evaluated.
Gelmi
M L
ML
Dipartimento di Ostetricia e Ginecologia, Università Cattolica, Roma, Italy.
Mottadelli
S
S
Pocar
D
D
Riva
A
A
Bombardelli
E
E
De Vincenzo
R
R
Scambia
G
G
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003078:Colchicine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D003078:Colchicine