N-Deacetyl-N-aminoacylthiocolchicine Derivatives:  Synthesis and Biological Evaluation on MDR-Positive and MDR-Negative Human Cancer Cell Lines

• Published in: Journal of medicinal chemistry 1999-12, Vol.42 (25), p.5272-5276
• Main Authors: Gelmi, Maria Luisa, Mottadelli, Sabrina, Pocar, Donato, Riva, Antonella, Bombardelli, Ezio, De Vincenzo, Rosa, Scambia, Giovanni
• Format: Article
• Language: English
• Subjects: Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Biological and medical sciences; Cell Division - drug effects; Colchicine - analogs & derivatives; Colchicine - chemical synthesis; Colchicine - pharmacology; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; General aspects; Humans; Magnetic Resonance Spectroscopy; Medical sciences; Pharmacology. Drug treatments; Tumor Cells, Cultured
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm981134e

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.