• Proceedings of the Plant Resources Society of Korea Conference
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• 2020.12a
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• pp.14-14
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• 2020

In December 2019, the COVID-19 epidemic was discovered in Wuhan, China, and since has disseminated around the world impacting human health for millions. Herein, in-silico drug discovery approaches were utilized to identify potential candidates as Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) main protease (M^pro) inhibitors. We investigated several databases including natural and natural-like products (>100,000 molecules), DrugBank database (10,036 drugs), major metabolites isolated from daily used spices (32 molecules), and current clinical drug candidates for the treatment of COVID-19 (18 drugs). All tested compounds were prepared and screened using molecular docking techniques. Based on the calculated docking scores, the top ones from each project under investigation were selected and subjected to molecular dynamics (MD) simulations followed by molecular mechanics-generalized Born surface area (MM-GBSA) binding energy calculations. Combined long MD simulations and MM-GBSA calculations revealed the potent compounds with prospective binding affinities against M^pro. Structural and energetic analyses over the simulated time demonstrated the high stabilities of the selected compounds. Our results showed that 4-bis([1,3]dioxolo)pyran-5-carboxamide derivatives (natural and natural-like products database), DB02388 and Cobicistat (DB09065) (DrugBank database), salvianolic acid A (spices secondary metabolites) and TMC-310911 (clinical-trial drugs database) exhibited high binding affinities with SARS-CoV-2 M^pro. In conclusion, these compounds are up-and-coming anti-COVID-19 drug candidates that warrant further detailed in vitro and in vivo experimental estimations.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1997.11a
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• pp.47-50
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• 1997

Drug development began with the finding of biologically active compounds which are obtained by chemical synthesis or from natural sources. The advent of Combinatorial Chemistry is recognized as a strategy which has a potential to change the methodology of research and development(R&D) of new drugs. Drug development has been carried out with diverse strategies. In the past several decades a variety of new methodology have been introduced in R&D. Random screening of accumulated synthetic samples which had been synthesized for development of other drugs led to the discovery of new drugs. The typical examples are anti-asthma drug trimethoquinol and calcium antagonist diltiazem. (herbesser). In particular the latter drug has been used as a calcium antagonist worldwide, however it was first synthesized to find new tranquilizer and this is the reason why diltiazem has benzodiazepam skeleton. The random screening contributed in the finding of new drugs were carried out with whole animal test and it is a standard methodology in R&D of new drugs. Aspirin is the first synthetic non-steroidal antiinflammatory drug(NSAID) and has been used for more than one hundred years. It is the first example of drug developed from natural product. Salicin is the main constituent of willow bark which had been used in Europe for a long time to treat arthritis and aspirin was developed from salicin. Most of NSAID used clinically were developed from the structure of aspirin, however it took 70 years to clarify why aspirin exhibits its antiinflammatory, analgesic and antipyretic activities. The target of aspirin is cyclooxygenase(COX)which is the first enzyme involved in arachidonate cascade leading to the production of prostaglandins(PG) and thromboxan(TX). Side effect of aspirin causing ulcer in stomach is rather serious problem, since aspirin is so popular drug easily obtained in drug store(OTP). This problem is now going to be solved by a new finding on COX, which have two different types, one is constitutionally expressed COX 1 in almost all organs and the other is inducible COX 2. COX 2 is the responsible enzyme in inflammation etc and now the search of COX 2 specific inhibitors is the target of R&D of next generation NSAID.

• Journal of Society of Preventive Korean Medicine
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• v.4 no.2
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• pp.258-272
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• 2000

The cytotoxic activities of Pinellia ternate, Aconitum carmichaeli, Arisaema amurense, Aconitum kusnezoffii and Scutellaria baicalensis on monkey kidney cell (Vero) and human liver cell (WRL68) were evaluated by Sulforhodamine B Protein (SRB) and Tetrazolium-based (MTT) colorimetric assay methods The results were as fellows : 1 The Pinellia ternate and Arisaema amurense did not show the cytotoxic activities at any concentration without processing or natural drugs. 2 The extracts of Aconitum carmichaeli, Aconitum kusnezoffii and Scutellaria baicalensis showed cytotoxic activities. However, the cytotoxic activities of processing drugs were less effective than the natural drugs. 3. The cytotoxic activities on monkey kidney cell (Vero) and human liver cell (WRL68) of Aconitum carmichaeli was determined by MTT assay. The Kyungpo(京?) of Aconitum carmichaeli showed less concentrate than that of the Dangpo(唐?). The $IC_{50}$ value on monkey kidney cell (Vero) and human liver cell (WRL68) of Kyungpo was $937{\pm}29\;and\;731{\pm}31{\mu}g/ml$, respectively 4. The cytotoxicity on monkey kidney cell (Vero) and human liver cell (WRL68) of Scutellaria baicalensis showed strong activities without processing or natural drugs.

• Korean Journal of Pharmacognosy
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• v.21 no.1
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• pp.100-102
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• 1990

Brine shrimp bioassay has been frequently utilized as a basic screening method for detecting a broad range of bioactive compounds from natural products. Each methanol, chloroform, and water extract of thirty-eight crude drugs were screened in the brine shrimp bioassay, and a number of crude drugs exhibited toxicity against brine shrimp nauplii.

• Journal of Microbiology and Biotechnology
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• v.28 no.10
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• pp.1716-1722
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• 2018

Immunosuppressive drugs are used to make the body less likely to reject transplanted organs or to treat autoimmune diseases. In this study, five immunosuppressive drugs including two glucocorticoids (dexamethasone and prednisolone), one calcineurin inhibitor (cyclosporin A), one non-steroid anti-inflammatory drug (aspirin), and one antimetabolite (methotrexate) were tested for their effects on viral proliferation using feline foamy virus (FFV). The five drugs had different cytotoxic effects on the Crandell-Ress feline kidney (CRFK) cells, the natural host cell of FFV. Dexamethasone-pretreated CRFK cells were susceptible to FFV infection, but pretreatment with prednisolone, cyclosporin A, aspirin, and methotrexate showed obvious inhibitory effects on FFV proliferation, by reducing viral production to 29.8-83.8% of that of an untreated control. These results were supported by western blot, which detected viral Gag structural protein in the infected cell lysate. As our results showed a correlation between immunosuppressive drugs and susceptibility to viral infections, it is proposed that immune-compromised individuals who are using immune-suppressive drugs may be especially vulnerable to viral infection originated from pets.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1998.11a
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• pp.114-117
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• 1998

Chinese traditional drugs have a long history to be used in clinics to treat various diseases and are confirmed to be effective approach through thousands of years of medical practice. Therefore, as a common understanding, the drug development from traditional Chinese medicines could be considered as a “shortcut” way with less blindness and more saving of time and money since development of new Chinese drugs has a different approach from that of western new drugs. Firstly, Chinese new drug development can be simplified as “from men to animal” process rather than “from animal to men” in western medicines. Hence the successful rate would be higher. Secondly, the original drugs or prescriptions from which the new drugs are planned to develop have been known what symptoms they are indicated for. Therefore, the developing procedure is actually a refine process with much less blindness than that of western drugs.

• Biomedical Science Letters
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• v.19 no.1
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• pp.32-40
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• 2013

Pluripotent stem cells (PSCs) have enormous potential in the biomedical sciences because they can grow continuously and differentiate into any kind of cell in the body. However, for future application in regenerative medicine, it is still a challenge to control the differentiation of PSCs without using genetic materials. To control the differentiation of PSCs, small molecules might be the best substitute for genetic materials considering the following advantages: small size, which enables penetration of plasma membrane; easy-to-modify structure; and low chance of genetic recombination in treated cells. Herein, we introduce small molecules that induce the neuroectodermal differentiation of mouse embryonic stem cells (ESCs). The small molecules were identified via ESC-based consecutive screenings of small-molecule libraries composed of 324 natural compounds or 93 selected drugs. The natural compounds discovered in the first screening were used to select 93 structurally similar drugs out of 1,200 approved drugs. In the second screening, among the 93 compounds, we found 4 drugs that induced the neuroectodermal differentiation of ESCs. These drugs were progesteroneor corticoid-derivatives. Our results suggest that small molecules targeting the progesterone receptor or glucocorticoid receptor could be used as chemical tools to induce the differentiation of PSCs into a specific germ lineage.

• Natural Product Sciences
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• v.21 no.4
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• pp.227-230
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• 2015

Chemical investigation of the fermentation broth of a Soft Coral-Derived fungus Pestalotiopsis sp., led to the isolation of a new phthalide derivative, pestalotiolide A (1), three known analogues (2, 3 and 4), along with 5'-O-acetyl uridine (5) first isolated as a natural product. The structure of the new compound (1) was established by comprehensive spectroscopic analysis and chemical methods. Compounds 1 - 4 possessed varying degrees of antiviral activities, which was reported for the first time. Compared to the positive control ribavirin ($IC_{50}=418.0{\mu}M$), pestalotiolide A (1) exhibited significant anti-EV71 activity in vitro, with an $IC_{50}$ value of $27.7{\mu}M$. Furthermore, the preliminary structure-activity relationship of antiviral activities was also discussed.

• YAKHAK HOEJI
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• v.12 no.3_4
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• pp.91-92
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• 1968

As the projects of this institute, 280 species of plants which are currently used as herb drugs in Korea were screened on the presence of alkaloids, phenolic compounds, flavonoids, chalcones, lactones, glycosides, carbohydrates, terpenoids, steroids, proteins, polypeptides, saponins, and organic acids, and the most reliable presence of alkaloids detected by thin layer chromatography is added by screening of 75 species.

• Korean Journal of Food Science and Technology
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• v.44 no.3
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• pp.356-361
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• 2012

Caffeine is a xanthine alkaloid derivative found in many foods and beverages. Dietary caffeine may interact with commonly-consumed over-the-counter (OTC) drugs in body. In this study, cytotoxic effects on the intestinal cells by combined treatment of caffeine with several OTC drugs, including ibuprofen, aspirin, and acetaminophen. Cytotoxic effect of caffeine was more potent in normal intestinal INT 407 cells than in colon cancer HCT 116 cells. Relative toxicity of caffeine and the OTC drugs was significantly enhanced in INT 407 cells when treated together. Intracellular thiol levels of the cells treated with the OTC drugs increased in the presence of caffeine. When HCT 116 cells were incubated with each OTC drug after or before caffeine treatment, the relative cytotoxicity of the OTC drugs increased. The present study may provide basic information about possible health effects through the interactions between caffeine and OTC drugs in the intestinal cells.