Cytotoxicity of enantiomers of gossypol Schiff's bases and optical stability of gossypolone.
Optical Schiff's bases of gossypol were prepared with chiral gossypol and ethylamine. As has been similarly observed among the gossypol enantiomers, the (-)-gossypol ethylimine was more active than either the (+)-gossypol ethylimine or the racemic gossypol ethylimine against KB and MCF7 cells. Gossypolone was also observed to be more toxic than gossypol against both cell lines. All of the gossypol products tested showed comparable toxicity toward MCF7/ADR (adriblastine-resistant) cells. Attempts at producing chiral gossypolone from chiral gossypol failed because of rapid racemization. In addition, the Schiff's base derivatives of gossypolone formed with R-(+)-2-amino-3-phenyl-1-propanol could only be separated at reduced temperature, indicating that gossypolone Schiff's bases are less optical stable than gossypol Schiff's bases.
Dao
Vi-Thuy
VT
Institut Curie, section recherche, transduction du signal et ontogénèse U528 INSERM, 75248 Paris, France.
Dowd
Michael K
MK
Martin
Marie-Thérèse
MT
Gaspard
Christiane
C
Mayer
Michel
M
Michelot
Robert J
RJ
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy*; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004317:Doxorubicin / Q000009:adverse effects; D005021:Ethylamines / Q000737:chemistry; D006072:Gossypol / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D007624:KB Cells / Q000187:drug effects; D013058:Mass Spectrometry; D012545:Schiff Bases / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013696:Temperature; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D005021:Ethylamines; D012545:Schiff Bases; C043259:gossypolone; D004317:Doxorubicin; D006072:Gossypol; C041564:ethylamine