N-Aminoacyl and N-hydroxyacyl derivatives of diosgenyl 2-amino-2-deoxy-β-d-glucopyranoside: Synthesis, antimicrobial and hemolytic activities.

Diosgenyl 2-amino-2-deoxy-β- d -glucopyranoside is a semisynthetic saponin with antimicrobial and antitumor activities. To search for more effective analogues, N -aminoacyl and N -hydroxyacyl derivatives of this saponin were synthesized conventionally and with microwave assistance, and tested against the human pathogenic fungi and Gram-positive and Gram-negative bacteria. None of the tested compounds exhibit activity against Gram-negative bacteria. Almost all of the synthesized N -aminoacyl saponins exhibit antifungal activity and act effectively against Gram-positive bacteria, some better than the parent compound. The best acting saponins are the same size and possess sarcosine or l - or d -alanine attached to the parent glucosaminoside. Shorter and longer aminoacyl residues are less advantageous. d -Alanine derivative is the most effective against Gram positive bacteria. Structure-activity relationship (SAR) analysis indicates that the free α-amino group in aminoacyl residue is necessary for antimicrobial activities of the tested saponins. (N -Acetyl)aminoacyl and N -hydroxyacyl analogs are inactive. Measurements of the hemolytic activities demonstrate that the best acting saponins are not toxic towards human red blood cells. [ABSTRACT FROM AUTHOR]