Synthesis and Potent Antileukemic Activities of N-Lactylsphingosine and N-Lactyldihydrosphingosine

• Published in: Journal of medicinal chemistry Vol. 46; no. 16; pp. 3445 - 3447
• Main Authors: Azuma, Hideki, Takao, Ryoko, Shikata, Keiji, Niiro, Hayato, Tachibana, Taro, Ogino, Kenji
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 31.07.2003; Amer Chemical Soc
• Subjects: Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; Apoptosis; Biological and medical sciences; Ceramides - chemical synthesis; Ceramides - pharmacology; Chemistry, Medicinal; General aspects; HL-60 Cells; Humans; Leukemia - drug therapy; Life Sciences & Biomedicine; Medical sciences; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Science & Technology; Sphingosine - analogs & derivatives; Sphingosine - chemical synthesis; Sphingosine - pharmacology; Stereoisomerism; Structure-Activity Relationship; SYMBIORAMIDE; APOPTOSIS; CELLS; L-SERINE; MITOCHONDRIA; SPHINGOSINE; SPHINGOLIPIDS; INDUCTION; CERAMIDE; Antineoplastic agent; Human; Aminoalcohol; Aliphatic compound; Leukemia; Cytotoxicity; In vitro; Biological activity; HL60 cell line; Cell line; Ceramide; Chemical synthesis; Tumor cell
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm030125p

N-(R)- and N-(S)-Lactylsphingosine and their corresponding dihydrosphingosine derivatives were synthesized. The antileukemic activities of these compounds were measured by MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) assay in human leukemia HL-60 cells. N-(R)- and N-(S)-Lactylsphingosine displayed higher activities than N-acetylsphingosine (C2-ceramide, a well-known apoptosis inducer), and their dihydrosphingosine derivatives had slight activities.