Cytotoxicity of enantiomers of gossypol Schiff’s bases and optical stability of gossypolone

• Published in: European journal of medicinal chemistry Vol. 39; no. 7; pp. 619 - 624
• Main Authors: Dao, Vi-Thuy, Dowd, Michael K, Martin, Marie-Thérèse, Gaspard, Christiane, Mayer, Michel, Michelot, Robert J
• Format: Journal Article
• Language: English
• Published: ISSY-LES-MOULINEAUX Elsevier Masson SAS 01.07.2004; Elsevier
• Subjects: Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Biological and medical sciences; Breast Neoplasms - drug therapy; Cell Survival - drug effects; Chemistry, Medicinal; Chromatography, High Pressure Liquid; Doxorubicin - adverse effects; Enantiomers; Ethylamines - chemistry; General aspects; Gossypol; Gossypol - analogs & derivatives; Gossypol - chemistry; Gossypol - pharmacology; Gossypolone; Humans; KB Cells - drug effects; Life Sciences & Biomedicine; Mass Spectrometry; MCF-7; MCF-7/ADR; Medical sciences; Multi-drug resistance; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Schiff Bases - chemical synthesis; Schiff Bases - chemistry; Schiff Bases - pharmacology; Science & Technology; Stereoisomerism; Structure-Activity Relationship; Temperature; Tumor Cells, Cultured; Gossypolone; Multi-drug resistance; MCF-7/ADR; MCF-7; KB; Enantiomers; Gossypol; multi-drug resistance; CANCER CELL; gossypolone; gossypol; CELL-LINES; ANTITUMOR; INHIBITION; enantiomers; DERIVATIVES; COLON-CARCINOMA; Antineoplastic agent; Cytotoxicity; Aldimine; Schiff base; Structure activity relation; Enantiomer; Multiple resistance; Bicyclic compound; Mammary gland; Chemical synthesis; Tumor cell; Human; Quinone; Naphthoquinone derivatives; Condensed benzenic compound; In vitro; Cell line; KB cell line
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2004.04.001

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.