• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.264.1-264.1
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• 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. (omitted)

• 통합자연과학논문집
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• 제8권3호
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• pp.153-163
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• 2015

Racemic synthesis of novel 5',5'-difluoro-2'-methyl-apiose nucleoside phosphonic acid analogs was achieved as potent antiviral agents. Phosphonation was performed by direct displacement of triflate intermediate with diethyl (lithiodifluoromethyl) phosphonate to give the corresponding (${\alpha},{\alpha}$-difluoroalkyl) phosphonate. Condensation successfully proceeded from a glycosyl donor with persilylated bases to yield the nucleoside phosphonate analogs. Deprotection of diethyl phosphonates provided the target nucleoside analogs. An antiviral evaluation of the synthesized compounds against various viruses such as HIV, HSV-1, HSV-2 and HCMV revealed that the pyrimidine analogs (cytosine, uracil, and thymine) have weak anti-HIV or HCMV activity.

• 대한수의학회지
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• 제40권3호
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• pp.471-478
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• 2000

새로운 항HIV 후보물질인 19개의 KR-V 경구제제의 생체이용률을 평가하기 위해 랫드에서 정맥 및 경구투여후 약물동태를 연구하였다. 혈장내 KR-V 화합물들의 검출은 HPLC-UVD 법을 이용하여 분석하였다. 19개 KR-V series 중 KR-V 3, 10, 14, 16 및 18-1만이 랫드에서 경구로 흡수되어 생체이용성을 나타내었다. 10mg/kg의 정맥투여후 약물 통태 연구에 있어서는 5개물질, KR-V3, 10, 14, 16 및 18-1의 소실 반감기는 서로 비슷하였으나 KR-V 3, 10, 14 및 16의 총청소율($CL_{total}$, >4L/hr/kg)은 KR-V 18-1(1.1L/hr/kg) 보다 유의성있게 높았다. KR-V 3, 10, 14 및 16에 비해 KR-V3 18-1이 혈중곡선하면적(AUC, $8.97{\mu}g{\cdot}hr/ml$)은 크고 겉보기분포용적(Vd, 0.58L/kg)은 적었다. 50mg/kg의 경구투여후 약물동태 연구에 있어서는 KR-V 18-1의 반감기가 다른 4개의 물질에 비해 비록 짧았지만 경구 AUC($3.659{\mu}g{\cdot}hr/ml$), 최고혈중농도($C_{max}$, $1.891{\mu}g/ml$) 는 현저히 높았다. 또한 별도의 in virus 실험결과 생체이용률을 나타낸 이들 5개의 물질들 중 KR-V 18-1만이 HIV-1 돌연변이종(mutants)에 대한 억제효과를 나타내었다. 따라서 KR-V 18-1이 항에이즈(AIDS)제의 새로운 후보물질 혹은 선도물질로서 가능성이 기대되었다.

• Tuberculosis and Respiratory Diseases
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• 제83권2호
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• pp.132-140
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• 2020

In human immunodeficiency virus (HIV)-infected patients, Pneumocystis jirovecii pneumonia (PCP) is a well-known opportunistic infection and its management has been established. However, PCP is an emerging threat to immunocompromised patients without HIV infection, such as those receiving novel immunosuppressive therapeutics for malignancy, organ transplantation, or connective tissue diseases. Clinical manifestations of PCP are quite different between patients with and without HIV infections. In patients without HIV infection, PCP rapidly progresses, is difficult to diagnose correctly, and causes severe respiratory failure with a poor prognosis. High-resolution computed tomography findings are different between PCP patients with HIV infection and those without. These differences in clinical and radiological features are due to severe or dysregulated inflammatory responses that are evoked by a relatively small number of Pneumocystis organisms in patients without HIV infection. In recent years, the usefulness of polymerase chain reaction and serum β-D-glucan assay for rapid and non-invasive diagnosis of PCP has been revealed. Although corticosteroid adjunctive to anti-Pneumocystis agents has been shown to be beneficial in some populations, the optimal dose and duration remain to be determined. Recent investigations revealed that Pneumocystis colonization is prevalent and that asymptomatic carriers are at risk for developing PCP and can serve as the reservoir for the spread of Pneumocystis by airborne transmission. These findings suggest the need for chemoprophylaxis in immunocompromised patients as well as infection control measures, although the indications remain controversial. Because a variety of novel immunosuppressive therapeutics have been emerging in medical practice, further innovations in the diagnosis and treatment of PCP are needed.

• Archives of Pharmacal Research
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• 제29권1호
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• pp.16-25
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• 2006

A novel series of 1-(1-benzofuran-2-yl-ethylidene)-4-substituted thiosemicarbazides (2a-d) along with some derived ring systems: substituted-2,3-dihydro-thiazoles(3a-c, 4a-f) and thiazolidin-4-ones(5a-d and 6a-d), were synthesized. In addition, cyanoacetic acid-(1-benzofuran-2-yl-ethylidene) hydrazide(7) was used to prepare another new series of compounds consisting of substituted pyridin-2(1H)-ones(8a-c); 2-thioxo-2,3-dihydro-thiazoles(9a-d) and 2-thioxo-2,3-dihydro-6H-thiazolo[4,5-d]pyrimidin-7-ones (10a-c, 11a-c). The absolute configuration of compound 5c was determined by X-ray crystallography. The compounds prepared were evaluated for their in vitro anti-HIV, anticancer, antibacterial, and antifungal activities. Among the tested compounds, compounds 5c and 9a produced a significant reduction ㅐ ㄹ the viral cytopathic effect (93.19% and 59.55%) at concentrations $>2.0{\times}10^{-4}\;M\;and\;2.5{\times}10^{-5}\;M$respectively. Compound 9a was confirmed to have moderate anti-HIV activity. Compounds 2a, 2d, and 5c showed mild antifungal activity. However, none of the tested compounds showed any significant anticancer activity.

• Bulletin of the Korean Chemical Society
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• 제31권8호
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• pp.2180-2184
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• 2010

We synthesized and tested the anti-HIV activity of the SATE prodrug of a 2'-methyl 5'-norcarbocyclic adenine analogue. The introduction of a methyl group in the 2'-position was performed by the addition of a carbonyl using isopropenyl magnesium bromide. The adenine base was efficiently coupled using the Mitsunobu reaction. The chemical stability study of the bis(SATE) derivative 18 was measured at neutral (pH 7.2) and slightly acid (milli-Q water, pH 5.5) pH, and compounds 16 and 18 were evaluated as potential anti-HIV-1 agents.

• Bulletin of the Korean Chemical Society
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• 제31권11호
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• pp.3348-3352
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• 2010

Novel 4'-ethyl-5'-norcarbocyclic adenosine phosphonic acid analogues were synthesized from propionaldehyde 5 through a de novo acyclic synthetic route using reiterative Grignard additions and ring-closing metathesis (RCM) as key reactions. The synthesized nucleoside phosphonic acids analogues 17, 18, 19, and 21 were subjected to antiviral screening against human immunodeficiency virus.

• Bulletin of the Korean Chemical Society
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• 제33권12호
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• pp.4007-4014
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• 2012

Efficient synthetic route to novel 4'-fluorinated 5'-deoxythreosyl phosphonic acid nucleosides was described from glyceraldehyde using Horner-Emmons reaction in the presence of triethyl ${\alpha}$-fluorophosphonoacetate. Glycosylation reaction of nucleosidic bases with glycosly donor 14 gave the nucleosides which were further phosphonated and hydrolyzed to reach desired nucleoside analogues. Synthesized nucleoside analogues 18, 21, 25 and 28 were tested for anti-HIV activity as well as cytotoxicity. Adenine derivatives 18 and 21 showed significant anti-HIV activity up to $100{\mu}M$.

• Bulletin of the Korean Chemical Society
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• 제29권9호
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• pp.1723-1728
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• 2008

An efficient synthetic route for carbocyclic versions of stavudine analogues and their evaluation on antiviral activity are described. The construction of an ethynylated quaternary carbon at the 4'-position of carbocyclic nucleosides was accomplished using Claisen rearrangement of 11 and ring-closing metathesis (RCM) of dienyne 14 as key transformations. An antiviral evaluation of the synthesized compounds, 20, 21, 22, and 25 against HIV-1, HSV-1, HSV-2, and HCMV showed that only the guanine analogue 25 is moderately active against HIV-1 in the MT-4 cell line ($EC_{50}$ = 11.91 $\mu$mol).

• 대한수의학회지
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• 제40권4호
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• pp.741-746
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• 2000

최근 새로 개발중인 항AIDS치료제 KR-V 시리즈를 대상으로 HPLC-UV 검출법을 이용해 랫드 혈장중에서 분석법을 검토하였다. 분석컬럼은 $C_{18}$($5{\mu}m$, $250{\times}2.0mm$ I.D.)을 이용하였으며 이동상은 물과 ACN의 혼합액(40/60, v/v)으로 하였다. 이상의 조건에서 모든 KR-V 물질들은 용출시간 4-12분에 비교적 신속하게 잘 분리되었으며 정량한계는 15-30 ng/ml, 혈장중 회수율은 KR-V 2, 7 및 15를 제외하고는 85%(C.V. <10%) 이상으로 나타내었다. Ester 구조를 포함하고 있는 KR-V 2, 7 및 15는 혈장중에서 극히 불안정하여 유도체 개발의 분자설계상 제외시키는 것이 좋을 것으로 사료되었다. 결론적으로 본 HPLC-UV 검출법온 KR-V 시리즈 물질들의 약물동태연구를 위한 약물 분석법의 유효한 방법으로 검토되었다.