The impact of sugar and fatty acid on the bioactivity of N-fatty acyl-L-tyrosine aglycone

Abstract

In the present study, a series of fatty acids-based (short, medium and long unsaturated chains) glycosylated N-fatty acyl-L-tyrosines and N-lipoyl-L-tyrosine methyl esters were synthesized and evaluated for their cytotoxic and antimicrobial activities. The aglycone moiety was synthesized using different chemical reagents. The glycosylation of aglycone moiety with different carbohydrates was performed using the Lewis acid, $$\hbox {BF}_{3.}\hbox {Et}_{2}\hbox {O}$$ . All the synthesized compounds were tested against a panel of four cancer cell lines. The glycosylated N-fatty acyl-L-tyrosines showed moderate activity against all the cell lines and the $$\hbox {IC}_{50}$$ values were in the range of $$15.6{-}45.6\;{\upmu }\hbox {M}$$ . However, the oleic acid analogues (10a, 10d) exhibited $$\hbox {IC}_{50}$$ values of 15.6, $$17.6\;{\upmu }\hbox {M}$$ , respectively, against MDA-MB-231 cell line. Glycosylated N-lipoyl-L-tyrosine methyl esters (6b–6d) showed promising activity against all the tested cell lines and the $$\hbox {IC}_{50}$$ values ranged between $$9.4{-}13.8\;{\upmu }\hbox {M}$$ . The compound 6d exhibited significant cytotoxicity and $$\hbox {IC}_{50}$$ values were 10.5, 9.4, 10.9 and $$12.1\;{\upmu }\hbox {M}$$ against A549, PC3, MDA-MB-231 and HepG2 cell lines, respectively. Moreover, the non-glycosylated N-fatty acyl-L-tyrosine and methyl N-fatty acyl-L-tyrosinate derivatives showed excellent and moderate antimicrobial activity against some of the tested bacterial strains. The glycosylated N-fatty acyl-L-tyrosines with short, medium and long chain unsaturated fatty acids and glycosylated N-lipoyl-L-tyrosine methyl esters were synthesized and further evaluated for their biological activities to examine the impact of sugar and fatty acid on the bioactivity of N-fatty acyl-L-tyrosine derivatives.