Synthesis of a novel series of 2-methylsulfanyl fatty acids and their toxicity on the human K-562 and U-937 leukemia cell lines.
The hitherto unknown 2-methylsulfanyldecanoic acid and 2-methylsulfanyldodecanoic acid were synthesized from methyl decanoate and methyl dodecanoate, respectively, through the reaction of lithium diisopropylamide and dimethyldisulfide in THF followed by saponification with potassium hydroxide in ethanol. Both alpha-methylsulfanylated FA were cytotoxic to the human chronic myelogenous leukemia K-562 and the human histiocytic lymphoma U-937 cell lines with EC50 values in the 200-300 microM range, which makes them more cytotoxic to these cell lines than decanoic and/or dodecanoic acid. The cytotoxicity of the studied FA toward K-562 followed the order 2-SCH3-12:0 > 2-SCH3-10:0 > 10:0 > 12:0 > 2-OCH3-12:0, whereas toward U-937 the cytotoxicity was 2-SCH3-10:0 > 2-SCH3-12:0 > 12:0 > 10:0 > 2-OCH3-12:0. These results indicate that the alpha-methylsulfanyl substitution increases the cytotoxicity of the C10 and C12 FA toward the studied leukemia cell lines.
Carballeira
Néstor M
NM
Department of Chemistry, University of Puerto Rico, San Juan 00931-3346. nmcarballeira@uprrp.edu
Miranda
Carlos
C
Orellano
Elsie A
EA
González
Fernando A
FA
D000677:Amsacrine / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D003652:Decanoic Acids / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D020014:K562 Cells; D007848:Laurates / Q000737:chemistry; D007850:Lauric Acids / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D013457:Sulfur Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D020298:U937 Cells
D000970:Antineoplastic Agents; D003652:Decanoic Acids; D005227:Fatty Acids; D007848:Laurates; D007850:Lauric Acids; D013457:Sulfur Compounds; D000677:Amsacrine; C030358:lauric acid; C031071:decanoic acid; C089549:lauric acid methyl ester