Improved enzymatic procedure for the synthesis of anandamide and N-fatty acylalkanolamine analogues and combination strategy in antitumor activity

PAULA G. QUINTANA; ROXANA M. GOROJOD; SANTIAGO N. CHANQUIA; ALICIA BALDESSARI; GUADALUPE GARCIA LINARES; MONICA L. KOTLER

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY

WILEY-V C H VERLAG GMBH

Lugar: Weinheim; Año: 2016 vol. 2016 p. 518 - 528

1434-193X

Twenty N-fatty acylamines from linolenic and arachidonic acids, fifteen of them new compounds, were obtained through Candida antarctica B lipase-catalyzed esterification and aminolysis reactions in very good yields and with high chemoselectivity. The optimal reaction conditions were achieved by studying the reaction parameters (temperature, E/S ratio, alcohol and alkanolamine/fatty acid ratio, time, solvent, free-solvent system, etc.). To identify ideal enzymatic methods for generating the alkanolamides we evaluated enzyme performance in three procedures: i) aminolysis of ethyl ester, ii) direct condensation between the fatty acid and the alkanolamine, and iii) a one-pot/two-step conversion of fatty acids into alkanolamides via in situ formation of the ethyl ester and subsequent aminolysis by the alkanolamine. The advantages noted with the enzymatic methodology, such as mild reaction conditions and low environmental impact, underscore biocatalysis as a convenient way to prepare the reported compounds. The cytotoxic activities of all compounds and mixtures of anandamide and its analogues were evaluated in rat glioma C6 cells. These studies reveal that some anandamide analogues enhance the antitumor effects of anandamide, suggesting their possible application as therapeutic tools in cancer treatment.