• Title/Summary/Keyword: anti-HIV agents

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Design and Synthesis of Novel 2'(β)-Fluoro-3'(α)-hydroxy-threose Nucleosides: Iso-FMAU Analogues as Potent Antiviral Agents

  • Kim, Seyeon;Jee, Jun-Pil;Hong, Joon Hee
    • Journal of Integrative Natural Science
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    • v.8 no.2
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    • pp.99-106
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    • 2015
  • Novel 2'(${\beta}$)-fluoro-3'(${\alpha}$)-hydroxy-threose nucleosides (iso-FMAU) as antiviral agents were designed and racemically synthesized from Solketal. Condensation successfully proceeded from a glycosyl donor 9 under $Vorbr{\ddot{u}}ggen$ conditions yielded the nucleoside analogues. Ammonolysis and hydrolysis of isopropylidene protection group gave the desired nucleoside analogues 12, 15, 18, and 19. The antiviral activities of the synthesized compounds were evaluated against the HIV-1, HSV-1, HSV-2 and HCMV. Compound 12 displayed some anti-HCMV activity ($EC_{50}=24.7{\mu}g/ml$) without exhibiting any cytotoxicity up to $100{\mu}M$.

An Efficient Synthesis of 4'-Vinylated Carbocyclic Nucleoside Analogues via Two Directional Ring-closing Metathesis

  • Li, Hua;Hong, Joon-Hee
    • Bulletin of the Korean Chemical Society
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    • v.29 no.5
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    • pp.993-997
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    • 2008
  • Two directional ring-closing metathesis (RCM) was applied successfully to the synthesis of 4'-vinylated carbocyclic nucleoside analogues from the trivinyl intermediate 12, which was readily made using a sequential Claisen rearrangement and ring-closing metathesis (RCM) starting from Weinreb amide 5. An antiviral evaluation of the synthesized compounds against various viruses such as HIV, HSV-1, HSV-2 and HCMV revealed that the guanine analogue 20 have moderate anti-HIV activity in the MT-4 cell line ($EC_{50}$ = 10.2 $\mu$ M).

An International Collaborative Program To Discover New Drugs from Tropical Biodiversity of Vietnam and Laos

  • Soejarto, Djaja D.;Pezzuto, John M.;Fong, Harry H.S.;Tan, Ghee Teng;Zhang, Hong Jie;Tamez, Pamela;Aydogmus, Zeynep;Chien, Nguyen Quyet;Franzblau, Scott G.;Gyllenhaal, Charlotte;Regalado, Jacinto C.;Hung, Nguyen Van;Hoang, Vu Dinh;Hiep, Nguyen Tien;Xuan, Le Thi;Hai, Nong Van;Cuong, Nguyen Manh;Bich, Truong Quang;Loc, Phan Ke;Vu, Bui Minh;Southavong, Boun Hoong
    • Natural Product Sciences
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    • v.8 no.1
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    • pp.1-15
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    • 2002
  • An International Cooperative Biodiversity Group (ICBG) program based at the University of Illinois at Chicago initiated its activities in 1998, with the following specific objectives: (a) inventory and conservation of of plants of Cuc Phuong National Park in Vietnam and of medicinal plants of Laos; (b) drug discovery (and development) based on plants of Vietnam and Laos; and (c) economic development of communities participating in the ICBG project both in Vietnam and Laos. Member-institutions and an industrial partner of this ICBG are bound by a Memorandum of Agreement that recognizes property and intellectual property rights, prior informed consent for access to genetic resources and to indigenous knowledge, the sharing of benefits that may arise from the drug discovery effort, and the provision of short-term and long-term benefits to host country institutions and communities. The drug discovery effort is targeted to the search for agents for therapies against malaria (antimalarial assay of plant extracts, using Plasmodium falciparum clones), AIDS (anti-HIV-l activity using HOG.R5 reporter cell line (through transactivation of the green fluorescent protein/GFP gene), cancer (screening of plant extracts in 6 human tumor cell lines - KB, Col-2, LU-l, LNCaP, HUVEC, hTert-RPEl), tuberculosis (screening of extracts in the microplate Alamar Blue assay against Mycobacterium tuberculosis $H_{37}Ra\;and\;H_{37}Rv),$ all performed at UIC, and CNS-related diseases (with special focus on Alzheimer's disease, pain and rheumatoid arthritis, and asthma), peformed at Glaxo Smith Kline (UK). Source plants were selected based on two approaches: biodiversity-based (plants of Cuc Phuong National Park) and ethnobotany-based (medicinal plants of Cuc Phuong National Park in Vietnam and medicinal plants of Laos). At mc, as of July, 2001, active leads had been identified in the anti-HIV, anticancer, antimalarial, and anti- TB assay, after the screening of more than 800 extracts. At least 25 biologically active compounds have been isolated, 13 of which are new with anti-HIV activity, and 3 also new with antimalarial activity. At GSK of 21 plant samples with a history of use to treat CNS-related diseases tested to date, a number showed activity against one or more of the CNS assay targets used, but no new compounds have been isolated. The results of the drug discovery effort to date indicate that tropical plant diversity of Vietnam and Laos unquestionably harbors biologically active chemical entities, which, through further research, may eventually yield candidates for drug development. Although the substantial monetary benefit of the drug discovery process (royalties) is a long way off, the UIC ICBG program provides direct and real-term benefits to host country institutions and communities.

Relationship between the Thyroid Hormone and Viral Infections in Pregnancy (임신 중 바이러스성 감염요인과 갑상선 호르몬의 상관성)

  • Lim, Dong-Kyu;Park, Chang-Eun
    • Korean Journal of Clinical Laboratory Science
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    • v.54 no.1
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    • pp.28-37
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    • 2022
  • Pregnancy requires an important interpretation of thyroid function tests. The presence of anti-thyroid antibodies and viral infectious agents affect the health of both the fetus and the mother. Hence, a selective evaluation of thyroid function in pregnancy is required. This study is a retrospective cross-sectional survey to examine the correlation between thyroid hormones and viral infections during pregnancy. The results showed that the triiodothyronine (T3) decreased with increasing age, especially in the hepatitis C virus (HCV)-positive group (P<0.01). In addition, although negative for the human immunodeficiency virus (HIV), thyroxine (FT4) showed a significant increase in near-threshold or twin pregnant women (P<0.05). The thyroid stimulating hormone (TSH) was highly distributed at the age of 30, and there was no statistically significant correlation with other viral infection factors. In addition, as a result of dividing and analyzing the result of TSH by the quantiles, FT4 and T3 showed a positive correlation but showed a negative correlation with TSH (P<0.05). Therefore, the evaluation of prenatal thyroid screening during pregnancy and viral infection factors should reflect the time of pregnancy, exposure to infection, and the quantitative values. Adequate thyroid hormone and viral infections availability is important for an uncomplicated pregnancy and optimal fetal development.

RNAi and miRNA in Viral Infections and Cancers

  • Mollaie, Hamid Reza;Monavari, Seyed Hamid Reza;Arabzadeh, Seyed Ali Mohammad;Shamsi-Shahrabadi, Mahmoud;Fazlalipour, Mehdi;Afshar, Reza Malekpour
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.12
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    • pp.7045-7056
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    • 2013
  • Since the first report of RNA interference (RNAi) less than a decade ago, this type of molecular intervention has been introduced to repress gene expression in vitro and also for in vivo studies in mammals. Understanding the mechanisms of action of synthetic small interfering RNAs (siRNAs) underlies use as therapeutic agents in the areas of cancer and viral infection. Recent studies have also promoted different theories about cell-specific targeting of siRNAs. Design and delivery strategies for successful treatment of human diseases are becomingmore established and relationships between miRNA and RNAi pathways have been revealed as virus-host cell interactions. Although both are well conserved in plants, invertebrates and mammals, there is also variabilityand a more complete understanding of differences will be needed for optimal application. RNA interference (RNAi) is rapid, cheap and selective in complex biological systems and has created new insight sin fields of cancer research, genetic disorders, virology and drug design. Our knowledge about the role of miRNAs and siRNAs pathways in virus-host cell interactions in virus infected cells is incomplete. There are different viral diseases but few antiviral drugs are available. For example, acyclovir for herpes viruses, alpha-interferon for hepatitis C and B viruses and anti-retroviral for HIV are accessible. Also cancer is obviously an important target for siRNA-based therapies, but the main problem in cancer therapy is targeting metastatic cells which spread from the original tumor. There are also other possible reservations and problems that might delay or even hinder siRNA-based therapies for the treatment of certain conditions; however, this remains the most promising approach for a wide range of diseases. Clearly, more studies must be done to allow efficient delivery and better understanding of unwanted side effects of siRNA-based therapies. In this review miRNA and RNAi biology, experimental design, anti-viral and anti-cancer effects are discussed.

Inhibitory Effects of Rosa rugosa Crude Extract and Solvent Fractions on Adipogenic Differentiation of 3T3-L1 Preadipocytes (해당화 추출물이 3T3-L1 지방세포 분화에 미치는 영향)

  • Lee, Hyunjung;Yang, Jiho;Choi, Mi-na;Jeon, Seongeun;Zhou, Xianrong;Oh, Jung Hwan;Karadeniz, Fatih;Seo, Youngwan;Kong, Chang-Suk
    • Journal of Life Science
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    • v.32 no.12
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    • pp.979-988
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    • 2022
  • Halophytes have been reported to possess a variety of physiological activities, such as anti-cancer, anti-oxidant, anti-diabetes, anti-inflammatory, and anti-obesity. Studies on the roots of the halophyte Rosa rugosa, in particular, have shown a variety of physiological activities and are known to be effective for nursing diabetic complications in traditional Korean medicine. In this study, the effect of R. rugosa on adipogenesis was investigated in 3T3-L1 pre-adipocytes treated with crude extract and solvent fractions (H2O, n-BuOH, 85% aq. MeOH, and n-Hex) obtained from R. rugosa roots. Treatment with extract and the solvent fractions inhibited the formation of intracellular lipid droplets in differentiated 3T3-L1 adipocytes compared to the untreated group. In particular, n-BuOH and 85% aq. MeOH fractions effectively decreased the expression of adipogenic transcription factors: peroxisome proliferator activated receptor-γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), and sterol regulatory element-binding protein 1c (SREBP1c) in both mRNA and protein levels. In conclusion, these results suggest that R. rugosa contains anti-adipogenic molecules that can be utilized as a nutraceutical against obesity. Further refining of n-BuOH and 85% aq. MeOH fractions and analysis of their action mechanisms could yield potential therapeutic agents with anti-adipogenic effects.

A study on dental hygiene department students' attitude toward infection in a dental hygiene workshop (치위생 실습실에서 치위생과 학생의 감염에 관한 태도 연구)

  • Kim, Eun-Hee;Kim, Seol-Ak
    • Journal of Korean society of Dental Hygiene
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    • v.9 no.4
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    • pp.849-863
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    • 2009
  • Objectives : This study was to study dental hygiene department students' management of infection and their attitude toward infection. Methods : This study was conducted from August 24, 2009 to September 20, 2009. 269 sophomore and junior college students enrolled in the department of dental hygiene from schools located in Gyeonggi-do and Gangwon-do participated in the study. A self-administered questionnaire survey was conducted. Results : 1. As for dental hygiene department students' recognition of the causes of infectious diseases, 80.7% of the respondents said hepatitis B was the infectious disease highly likely to occur in laboratories. 35.3% was correct about the antecedent variables of infection in the workshop, 24.9% about the oral symptoms of HIV and 18.6% about the diseases induced by HBV. The recognition rates were generally low. 2. About whether the respondents ask patients questions about infectious diseases, 80.7% of them answered Yes, but only 56.2% of them said they do so every time, and 17.8% of them said they never do so. 3. As far as washing hands to prevent infectious diseases is concerned, 97.4% of the respondents said hand washing helps prevent infection. 72.5% of them said they wash their hands every time before they practice on a patient, while 84.0% of them said they washed their hands after the lab practice. 90.7% said they use liquid soap containing anti-microbial agents, and 81.8% of them said they use paper towels. 4. With regard to protective gear for prevention of infectious diseases, 98.9% of the respondents said it is desirable to use disposable protective gear for each patient. When it comes to what they actually used as protective gear, 91.1% said aprons, 89.2% gloves, and 87.7% masks. However, a low percentage of the respondents actually use goggles and replace masks when they got damp, 11.2% and 24.2% respectively. Conclusions : As for treating the surface of equipments to prevent infectious diseases, most of the respondents exhibited a high recognition rate. Relative fewer respondents actually treat the surface of equipments than those respondents who are aware of the need to do so. A high percentage of the respondents also said they use alcohol sponge to treat the surface of each equipment in order to prevent infectious diseases.

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