• Journal of Integrative Natural Science
• /
• v.8 no.1
• /
• pp.48-55
• /
• 2015

Novel 2'(${\beta}$)-methyl-5'-deoxyapiose purine phosphonic acid analogues were designed and synthesized from 2-propanone-1,3-diacetate. Condensation successfully proceeded from a glycosyl donor 9 under Vorbr${\ddot{u}}$ggen conditions. Condensation of aldehyde 14 with Wittig reagent [(diethoxyphosphinyl)methylidene] triphenylphosphorane gave the desired nucleoside phosphonate analogues 15. Ammonolysis and hydrolysis of phosphonates gave the nucleoside phosphonic acid analogue 17 and 19. The synthesized nucleoside analogues were subjected to antiviral screening against HIV-1. The adenine analogue 19 exhibited weak in vitro activities against HIV-1.

• Bulletin of the Korean Chemical Society
• /
• v.34 no.12
• /
• pp.3621-3628
• /
• 2013

Novel 5'-deoxythreosyl purine phosphonic acid analogues containing a 2'-electropositive moiety such as fluorine atom, were designed and synthesized from commercially available 1,3-dihydroxy acetone. Condensation successfully proceeded from a glycosyl donor 6 under Vorbr$\ddot{u}$ggen conditions and cross-metathesis gave the desired phosphonate analogues 7a, 7b, 17a and 17b. The synthesized nucleoside phosphonic acid analogues 13, 16, 23, 26, 28 were subjected to antiviral screening against HIV-1. The bis(SATE) adenine analogue 28 exhibited significant in vitro activities against HIV-1.

• Bulletin of the Korean Chemical Society
• /
• v.35 no.9
• /
• pp.2743-2748
• /
• 2014

Novel 4'-trifluoromethyl-5'-norcarbocyclic purine phosphonic acid analogs were efficiently synthesized from commercially available 1,3-dihydroxy cyclopentane (5). Trifluoromethylation was successfully performed by using the Ruppert-Prakash reaction. The purine nucleosidic bases were efficiently coupled by using the Mitsunobu reaction. The synthesized adenosine phosphonic acids analogs 13 and 16 were screened for antiviral activity against human immunodeficiency virus-1 (HIV-1). Adenine derivative 13 exhibited significant anti-HIV-1 activity.

• Korean Journal of Pharmacognosy
• /
• v.34 no.1 s.132
• /
• pp.28-32
• /
• 2003

In order to search for the anti-HIV agents from natural products, eighty MeOH extracts of medicinal plants were applied to a syncytia formation inhibition assay which is based on the interaction between the HIV-1 envelope glycoprotein gp120/gp41 and the cellular membrane protein CD4 of T lymphocytes. Among them, Ailanthus altissima showed a potent virus-cell fusion inhibitory activity. Repeated column chromatoghaphy of the methylene chloride fraction of A. altissima afforded compounds 1$({\beta}-sitosterol-3-O-{\beta}-D-glucoside)$, 2(tetramethoxycoumarin), and 3(ocotillone). Virus-cell fusion inhibitory activity of compound 3(ocotillone) was $70.76{\pm}4.09%$ at the concentration of $100\;{\mu}g/ml$.

• Bulletin of the Korean Chemical Society
• /
• v.32 no.8
• /
• pp.2689-2694
• /
• 2011

Novel 5'-norcarbocyclic adenine and guanine phosphonic acid analogues with 6'-electronegative moiety such as unsaturated C-C bond were designed and synthesized from commercially available 2-methylene-propane-1,3-diol (4). Regioselective Mitsunobu reaction successfully proceeded from an allylic functional group (${\pm}$)-12b at low reaction temperature in polar cosolvent (DMF/1,4-dioxane) to give purine phosphonate analogues (${\pm}$)-13 and (${\pm}$)-20. The purine nucleoside phosphonate and phosphonic acid analogues were subjected to antiviral screening against HIV-1. Guanine analogue (${\pm}$)-23 shows significant anti-HIV activity in PBM cell lines ($EC_{50}=8.1\;{\mu}M$).

• Bulletin of the Korean Chemical Society
• /
• v.32 no.2
• /
• pp.411-416
• /
• 2011

Steric and electronic parameters of 4'-substituents play significant roles in steering the conformation of nucleoside analogues. In order to investigate the relationship of 4'-group with antiviral enhancement, novel 4'-hydroxymethyl-5'-norcarbocyclic adenosine phosphonic acid analogues were designed and synthesized from 2,2-dimethyl-1,3-dioxolane-4-ethanol (5) using reiterative Grignard addition and ring-closing metathesis (RCM) as key reactions. The synthesized adenosine phosphonic acids analogues (22) and (23) were subjected to antiviral screening against HIV-1. Compound (23) exhibited moderate anti-HIV activity ($EC_50$ = 8.61 ${\mu}M$) in the CEM cell line.

• The Korea Journal of Herbology
• /
• v.21 no.4
• /
• pp.115-121
• /
• 2006

Objectives : For the purpose of developing new anti-HIV agents from natural sources, the extracts of Actinidia arguta were tested for their inhibitory effects on essential enzymes as the reverse transcriptase (RT), protease and ${\alpha}-\;glucosidase$. And we predicted inhibition activity of major compounds of Actinidia arguta using Quantitative Structure Activity Relationships (QSAR). Methods : In this assay the activity of HIV-1 reverse transcriptase is measured as the formation of a strand of copy-DNA (cDNA) using RNA as a template. The activity of HIV-1 protease is measured as the cleavage of an oligopeptide by HIV-1 protease. Results : In the anti-HIV-1 RT using Enzyme Linked Oligonucleotide Sorbent Assay (ELOSA) method, water extracts (100ug/ml) of stem and leaf showed strong activity of 93.9% and 91.9%, respectively. In the HIV-1 protease inhibition assay, aqueous stem extract inhibited the activity of the enzyme to cleave an oligopeptide, resembling one of the cleavage sites in the viral polyprotein which can only be processed by HIV-1 protease with 56.8%. In the ${\alpha}-glucosidase$ inhibition assay, aqueous stem extract showed activity of 73.1%. Conclusion : We found out this result, for these samples it is possible that the inhibition of the viral replication in vitro is due to the inhibition at least one of RT and ${\alpha}-glucosidase$. It would be of great interest to identify the compounds which are responsible for this inhibition, since all therapeutically useful agent up to date are RT, PR and ${\alpha}-glucosidase$ inhibitors.

• Natural Product Sciences
• /
• v.4 no.4
• /
• pp.241-244
• /
• 1998

For the development of anti-AIDS agents, thirty-seven methanol extracts of Korean plant materials were tested for their inhibitory effects on human immunodeficiency virus type-1 (HIV-1) protease. Extracts of seven plants showed more than 30% inhibitory activities on HIV-1 protease at a concentration of $100\;{\mu}g/ml$. The bark of Berchemia berchemiaefolia, the leaf of Lindera erythrocarpa and the whole plant of Siegesbeckia pubescens exhibited significant inhibititory activities on HIV-1 protease with 56.2, 50.8, and 46.6%, respectively.

• YAKHAK HOEJI
• /
• v.47 no.1
• /
• pp.46-51
• /
• 2003

Baicalein and baicalin are flavonoid compounds isolated from medicinal herb Scutellaria baicalensis Georgi (Labiatae) and have been known to possess antiviral activities. In the present study, we investigated the in vitro effects of baicalein and baicalin on the three distinctive enzymatic activities of the human immunodeficiency virus type-1 (HIV-1) integrase-endonucleolytic, integration, and disintegration activities. Both compounds inhibited the three enzymatic activities in a dose-dependent manner. The 50％ inhibitory concentrations of baicalein and baicalin for endonucleolytic activities of HIV-1 integrase were 4.4$\pm$3.3 and 25.9$\pm$4.0$\mu$M, respectively. In general, baicalein exhibited nearly 6- to 10-fold stronger inhibition than baicalin for the three enzymatic activities. These data demonstrate that baicalein or baicalin can be used as a leading compound to develop anti-AIDS chemotherapeutic agents targeting to the HIV-1 integrase.

• Archives of Pharmacal Research
• /
• v.28 no.10
• /
• pp.1105-1110
• /
• 2005

Novel anomeric branched carbocyclic nucleosides were synthesized from 1,3-dihydroxy acetone. 4'-Hydroxymethyl was installed by [3,3]-sigmatropic rearrangement reaction and 1'-methyl group was introduced by carbonyl addition of methylmagnesium bromide. The coupling of nucleosidic bases and desilylation afforded a series of novel nucleosides. The synthesized compounds $16{\~}19$ were evaluated for their antiviral activity against HIV-1, HSV-1, HSV-2, and EMCV. Compounds 16 and 19 exhibit toxicity non-related to any anti-HIV-1 activity.