ABSTRACT
A new method for the synthesis of glycyrrhizic acid (GA) conjugates with S-benzyl-L-cysteine using 1-ethyl-3-(3-dimethylaminoproopyl)carbodiimide is proposed. It is established that 3-O-{2-O-[N-(ß-D-glucopyranosyluronyl)-L-cysteine-S-benzyl]-N-(ß-D-glucopyranosyluronyl)-L-cysteine-S-benzyl}-(3ß,20ß)-11-oxo-30-(N-carbonyl-L-cysteine-S-benzyl)-30-norolean-12-ene is superior to GA in inhibiting the accumulation of HIV-I virus-specific protein p24 (viral antigen) in MT-4 cell culture (IC50 3 µg/mL, SI 90) and is 50 - 55 times less toxic to cells than azidothymidine.
ABSTRACT
The glycyrrhizic acid (GA) analog olean-9(11),12(13)-dien-30-oic acid 3ß-(2-O-ß-D-glucuronopyranosyl-ß-D-glucuronopyranoside) (II) was synthesized via reduction of GA by NaBH4 in refluxing 2-PrOH:H2O with subsequent work up with HCl (5%). The cytotoxicity and antiviral activity of this glycoside against HIV-1 was studied in MT-4 cell culture. It was found that II was practically non-toxic for MT-4 cells while inhibiting accumulation of virus-specific protein p24 and RNA-dependent DNA-polymerase activity of HIV-1 reverse transcriptase (RT) (IC50 3.1 ±1.0 µg/mL).
ABSTRACT
New conjugates of 18ß- and 18α-glycyrrhizic acids (GAs) each containing two di- or α-methyl esters of L-aspartic acid in the carbohydrate part of the glycosides were synthesized by the activated ester method using the N-hydroxysuccinimide (HOSu) and N,N'-dicyclohexylcarbodiimide. It was found that the conjugate of 18ß-GA with Asp(OMe)(OMe) (4) at a concentration of 250 µg/mL inhibited effectively RT of HIV-1 and the accumulation of virus antigen p24 in MT-4 cell culture (95-97 %) and protected cells from the cytopathogenic action of the virus.
ABSTRACT
New esters (sulfate, nicotinates, and 4-methoxycinnamate) of 18α-glycyrrhizic acid (18α-GA) were synthesized; these were D/E-trans-isomers of natural 18ß-GA (GA), which is the major triterpene glycoside in the roots of Spanish licorice and Urals licorice (Glycyrrhiza glabra L. and Gl. uralensis Fisher). Changes in the stereochemistry of the GA aglycone led to significant decreases in its anti-HIV-1 activity.
ABSTRACT
The review is devoted to the problem of creating new antiviral drugs based on glycyrrhizic acid (GA), the major triterpene glycoside extracted from roots of common and Ural licorice (Glycyrrhiza glabra L. and G. uralensis Fisher, respectively). Published data on the natural GA sources, antiviral activity of GA and its derivatives, clinical applications of GA-based drugs, and the properties of GA-containing biologically active nutrient additives are summarized. Possible mechanisms of the antiviral activity of GA and its derivatives are examined. It is shown that chemical modification of GA is a promising way of designing new highly active antiviral drugs for the prophylaxis and treatment of HIV, hepatitis B and C, corona-virus, and herpes simplex virus infections.
