Evaluation of long-term treatment with glycyrrhizin and of combination therapy with glycyrrhizin and AZT or DDI on HIV-1 carriers

Ikegami, Nobuyuki; Kinoshita, S.; Kanesaki, T.; Uno, Katsuji; Akatani, Kaoru; Kishida, Teruji

doi:10.1016/0166-3542(96)80279-8

Cited by 7 publications

(5 citation statements)

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“…The full or selective esterification of hydroxyl groups of the carbohydrate part of GL, its salts or trimethyl ester (17) was carried out using chlorides of various aromatic acids in pyridine, pyridine -triethylamine or pyridine -tributylamine to form esters (27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42) [66,67].…”

Section: Synthesis Of Glycyrrhizic Acid Estersmentioning

confidence: 99%

“…It has been demonstrated by clinical studies in Japan that the administration of GL (SNMC) to AIDS patients had resulted in delaying the progression of HIV infection symptoms [37]. Monotherapy with GL started earlier in the asymptomatic HIV-1 carrier patients has been effective to maintain their state for more than 11 years without induction of drug resistance [38]. It was found that the introduction of GL together with azidothymydine (AZT) (zidovudine) to AIDS patients has decreased the side-effects of the later [39,40].…”

Section: Introductionmentioning

confidence: 99%

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Chemical Modification of Glycyrrhizic Acid As A Route to New Bioactive Compounds for Medicine

Балтина

2003

CMC

223

160

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Glycyrrhizic Acid (GL) is the major bioactive triterpene glycoside of licorice root (Glycyrrhiza Radix) extracts possessing a wide range of pharmacological properties (anti-inflammatory, anti-ulcer, anti-allergic, anti-dote, anti-oxidant, anti-tumor, anti-viral etc.). Official sources of GL are Glycyrrhiza glabra L. and Gl. uralensis Fish. (Leguminosae). The content of GL in licorice root is 2-24% of the dry weight. GL is one of the leading natural compounds for clinical trials of chronic active viral hepatitis and HIV infections (preparation Stronger Neo-Minophagen C, SNMC), and its monoammonium salt (glycyram, tussilinar) is used as an anti-inflammatory and anti-allergic remedy. The synthetic transformations of GL on carboxyl and hydroxyl groups were carried out to produce new bioactive derivatives for medicine. GL esters were produced containing fragments of bioactive acids (4-nitrobenzoic, cinnamic, salycilic, acetylsalycilic, nicotinic, isonicotinic). Bioactive amides of GL were synthesized using chloroanhydride technique and N,N'-diciclohexylcarbodiimide (DCC) method. The synthesis of acylthioureids and semicarbazones was carried out via the reaction of triacylisothiocianate of penta-O-acetyl-GL with primary amines and hydrazines. The chain of transformations of trichloranhydride of penta-O-acetyl-GL was made with the introduction of diazoketone groups in the molecule. A new group of GL derivatives to be triterpene glycopeptides was prepared by the activated esters method (N-hydrohysuccinimide-DCC or N-hydroxybenzotriazol-DCC) using alkyl (methyl, ethyl, propyl, butyl, tert-butyl) or benzyl (4-nitrobenzyl) esters of amino acids. The glycyrrhizyl analogs of the known immunostimulator, N-acetyl-muramoyldipeptide (MDP), were synthesized using Reagent Woodward K. A series of ureids and carbamates of GL was synthesized containing 5-amino-5-desoxy-D-xylopyranose units. The synthesis of 4-nitro-4-desoxy-glycosides, modified analogs of GL, was carried out by the oxidative splitting of the carbohydrate part of GL with NaIO(4). Triterpene 2-desoxy-D-glycosides, analogs of GL, were prepared by the glycal method in the presence of iodine-containing promoters or sulfonic acid cation-exchange resin KU-2-8 (H+) and LiBr. New anti-inflammatory and anti-ulcer agents were found among GL derivatives such as esters, amides, ureids, carbamates, thioureids and glycopeptides. GL glycopeptides are of interest as immunomodulators. Some of the chemically modified GL derivatives (salts, amides, glycopeptides) were potent HIV-1 and HIV-2 inhibitors in vitro. Preparation niglizin (penta-O-nicotinate of GL) was studied clinically as an anti-inflammatory agent and is of interest for studies as hepatoprotector and HIV inhibitor.

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Section: Synthesis Of Glycyrrhizic Acid Estersmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Chemical Modification of Glycyrrhizic Acid As A Route to New Bioactive Compounds for Medicine

Балтина

2003

CMC

223

160

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“…[ 30 , 31 , 34 , 35 ], and is used clinically for the treatment of chronic viral hepatitis B and C in Japan and China (SNMC preparation, Compound Glycyrrhizin Ingecpion Injection, Compound Glycyrrhizin Ingecpion Tablets) [ 31 , 32 , 36 ]. GL inhibits the reproduction of HIV-1 in vitro and in vivo and is suitable for the long-term therapy of HIV infection in a combination with other anti-HIV agents [ 37 , 38 ]. GL affects cellular factors such as protein kinase II, casein kinase II and transcription factors (activating protein I and nuclear factor kB) [ 31 , 32 , 33 ].…”

Section: Introductionmentioning

confidence: 99%

Glycyrrhizic Acid Derivatives Bearing Amino Acid Residues in the Carbohydrate Part as Dengue Virus E Protein Inhibitors: Synthesis and Antiviral Activity

Hour

Chen

Lin

et al. 2022

IJMS

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Dengue virus (DENV) is one of the most geographically distributed mosquito-borne flaviviruses, like Japanese encephalitis virus (JEV), and Zika virus (ZIKV). In this study, a library of the known and novel Glycyrrhizic acid (GL) derivatives bearing amino acid residues or their methyl/ethyl esters in the carbohydrate part were synthesized and studied as DENV inhibitors in vitro using the cytopathic effect (CPE), viral infectivity and virus yield assays with DENV1 and DENV-2 in Vero E6 and A549 cells. Among the GL conjugates tested, compound hits GL-D-ValOMe 3, GL-TyrOMe 6, GL-PheOEt 11, and GL-LysOMe 21 were discovered to have better antiviral activity than GL, with IC50 values ranging from <0.1 to 5.98 μM on the in vitro infectivity of DENV1 and DENV2 in Vero E6 and A549 cells. Compound hits 3, 6, 11, and 21 had a concentration-dependent inhibition on the virus yield in Vero E6, in which GL-D-ValOMe 3 and GL-PheOEt 11 were the most active inhibitors of DENV2 yield. Meanwhile, the time-of-addition assay indicated that conjugates GL-D-ValOMe 3 and GL-PheOEt 11 exhibited a substantial decrease in the DENV2 attachment stage. Subsequently, chimeric single-round infectious particles (SRIPs) of DENV2 C-prM-E protein/JEV replicon and DENV2 prM-E/ZIKV replicon were utilized for the DENV envelope I protein-mediated attachment assay. GL conjugates 3 and 11 significantly reduced the attachment of chimeric DENV2 C-prM-E/JEV and DENV2 prM-E/ZIKV SRIPs onto Vero E6 cells in a concentration-dependent manner but did not impede the attachment of wild-type JEV CprME/JEV and ZIKV prM-E/ZIKV SRIPs, indicating the inhibition of Compounds 3 and 11 on DENV2 E-mediated attachment. Molecular docking data revealed that Compounds 3 and 11 have hydrophobic interactions within a hydrophobic pocket among the interfaces of Domains I, II, and the stem region of the DENV2 envelope (E) protein. These results displayed that Compounds 3 and 11 were the lead compounds targeting the DENV E protein. Altogether, our findings provide new insights into the structure–activity relationship of GL derivatives conjugated with amino acid residues and can be the new fundamental basis for the search and development of novel flavivirus inhibitors based on natural compounds.

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“…In contrast with azidothymidine, I and its derivatives at active concentrations were nontoxic to MT-4 cells [89]. It was shown that simultaneous administration of I and azidothymidine to AIDS patients reduced side effects of the latter [91].…”

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confidence: 99%

Prospects for the creation of new antiviral drugs based on glycyrrhizic acid and its derivatives (a review)

et al. 2009

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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.

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Evaluation of long-term treatment with glycyrrhizin and of combination therapy with glycyrrhizin and AZT or DDI on HIV-1 carriers

Cited by 7 publications

References 0 publications

Chemical Modification of Glycyrrhizic Acid As A Route to New Bioactive Compounds for Medicine

Chemical Modification of Glycyrrhizic Acid As A Route to New Bioactive Compounds for Medicine

Glycyrrhizic Acid Derivatives Bearing Amino Acid Residues in the Carbohydrate Part as Dengue Virus E Protein Inhibitors: Synthesis and Antiviral Activity

Prospects for the creation of new antiviral drugs based on glycyrrhizic acid and its derivatives (a review)

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