Synthesis and Immunostimulating Activity of Cysteine-Containing Derivatives of Glycyrrhizic Acid

Abstract

New cysteine-containing derivatives of glycyrrhizic acid were synthesized by its coupling with Cys(Bzl) esters or the Cys(Bzl)-Val-OBu(t) dipeptide by the active ester method (DCC/HOSu) or by Woodward's reagent K. The derivatives with Cys(Bzl) and Cys(Bzl)-Val residues attached to the carbohydrate part of the molecule stimulated the primary immune response and the reaction of delayed-type hypersensitivity in mice at a dose of 2 mg/kg. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no. 1; see also http://www.maik.ru.

Glycyrrhizin and glycyrrhetic acid: scaffolds to promising new pharmacologically active compounds

“…Compounds 18 and 22, administered intraperitonially, presented an imunostimulating activity in mice, increasing the number of antibody-producing cells when compared to control (isotonic saline solution) animals. 7 Another work from the same group yielded GL-aminoacid ester derivatives 22-32 (Scheme 3) in a similar fashion. Compounds 23, 26 and 29, administered intraperitonially, presented in vivo immunomodulating activity, increasing the serum level of agglutinins and hemolysins when compared to control (isotonic saline solution) animals.…”

“…Compounds 23, 26 and 29, administered intraperitonially, presented in vivo immunomodulating activity, increasing the serum level of agglutinins and hemolysins when compared to control (isotonic saline solution) animals. 8 Although other compounds in both series were not tested, the chemical modifications performed may indicate that the esterification of glucosyl carboxylic groups of GL with aminoacid derivatives such as Cyz(Bz)OH, Cyz(Bz)-Val(OH), glycine ethyl ester, alanine butyl ester or valine butyl ester, with the C-30 carboxyl group either unmodified or esterified with methyl groups lead to immunostimulating compounds. In one case, esterification of the three carboxyl groups of GL with glutamic acid methyl ester lead to an immunostimulating compound (5), whereas the derivative with only the glucosyl acid groups esterified (12) lead to an immunosupressor compound, which indicates that the carboxyl group of this aminoacid derivative is important for the interaction of the compound with its molecular target.…”

Synthesis and anti-HIV-1 activity of new conjugates of 18β- and 18α-glycyrrhizic acids with aspartic acid esters

“…We found among them promising immunomodulators, inhibitors of Epstein-Barr virus and SARS-associated coronaviruses, and anti-HIV-1 agents [3][4][5][6][7].…”

Synthesis of glycyrrhizic acid conjugates containing L-lysine

“…We have previously synthesized glucopeptide conjugates (GC) with various amino acids and dipeptides, among which were found stimulators of the primary immune response [3][4][5] and anti-inflammatory, antiulcer, and anti-HIV agents [6][7][8].…”

“…In continuation of our research on the synthesis of new biologically active GA derivatives, we synthesized new conjugates (2)(3)(4)(5)(6)(7)(8) with an amide bond formed through the α-NH 2 group of N ε -carbobenzyloxy-L-lysine or its esters containing two or three amino components. Lys(Z)-OH = C 6 H 5 CH 2 OCONH 5 CH 2 4 CH 2 3 CH 2 2 CH 2 1 CH(COOH)NH-Conjugate 2 was synthesized by condensation of GA with the trifluoroacetate of N ε -carbobenzyloxy-L-lysine methyl ester [Lys(Z)-OMe·CF 3 COOH] using N-hydroxybenzotriazole (HOBt)-N,N′-dicyclohexylcarbodiimide (DCC) in the presence of triethyloamine (Et 3 N) as described previously [9].…”