• Bulletin of the Korean Chemical Society
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• v.32 no.9
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• pp.3219-3222
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• 2011

Three types of ${\beta}$-ketoacyl acyl carrier protein synthase (KAS) are important for overcoming the bacterial resistance problem. Recently, we reported the discovery of a antimicrobial flavonoid, YKAF01 (3,6-dihydroxyflavone), which exhibits antibacterial activity against Gram-positive bacteria through inhibition of ${\beta}$-ketoacyl acyl carrier protein synthase III (KAS III). In this report, we suggested that YKAF01 can be an inhibitor ${\beta}$-ketoacyl acyl carrier protein synthase I (KAS I) with dual inhibitory activity for KAS I as well as KAS III. KAS I is related to the elongation of unsaturated fatty acids in bacterial fatty acid synthesis and can be a good therapeutic target of designing novel antibiotics. We performed docking study of Escherichia coli KAS I (ecKAS I) and YKAF01, and determined their binding model. YKAF01 binds to KAS I with high binding affinity ($2.12{\times}10^6$) and exhibited an antimicrobial activity against the multidrug-resistant E. coli with minimal inhibitory concentration (MIC) value of 512 ${\mu}g$/mL. Further optimization of this compound will be carried out to improve its antimicrobial activity and membrane permeability against bacterial cell membrane.

• KSBB Journal
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• v.29 no.3
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• pp.210-219
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• 2014

Sayuksan has been widely applied to treat a variety of diseases such as acute hepatitis, gastritis, and colitis. Sayuksan consists of medicinal herbs such as Glycrrhizae uralensis Fischer, Paeonia lactiflora Pallas, Bupleurum falcatum Linne, and Poncirus trifoliata Rafinesqul. Methanol extracts (1 mg/mL) from the four kinds of medicinal herbs did not show antibiotic activities against general test strains and multi-drug resistant strains. The antibacterial activity of fermented medicinal herbs extracts with Lactobacillus spp. strain was confirmed as Gram-positive bacteria which are higher than Gram-negative bacteria. Extracts of Glycrrhizae uralensis Fischer fermented with Lb. casei KCTC 3109 displayed inhibitory diameters of 16 mm against Pseudomonas aeruginosa P01828. Superoxide dismutase (SOD)-like activity of the medicinal herb extracts was not determined, but the extract of Paeonia lactiflora Pallas fermented with six strains of Lactobacillus spp. had the highest antioxidant activity. SOD-like activity of Paeonia lactiflora Pallas extracts fermented by Lb. brevis KCTC 3498 was $41.4{\pm}0.8%$, which was the highest antioxidant activity among the fermented extracts with the other medicinal herbs.

• BMB Reports
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• v.29 no.4
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• pp.314-320
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• 1996

The effects of non-cytotoxic concentrations of tamoxifen, verapamil, and trifluoperazine on doxorubicin cytotoxicity in five human breast cancer cell lines were studied. A non-cytotoxic concentration of tamoxifen resulted in enhanced doxorubicin cytotoxicity in HTB-123, HTB-26, and MCF-7. In these three cell lines, a combination of tamoxifen with verapamil resulted in even more increased doxorubicin cytotoxicity. Addition of verapamil or trifluoperazine alone did not influence the doxorubicin cytotoxicity significantly. Only in HTB-19 did coincubation with verapamil increase the doxorubicin cytotoxicity. In HTB-123, combination of tamoxifen with trifluoperazine increased the doxorubicin cytotoxicity significantly. In the cell lines where co-incubation with tamoxifen increased doxorubicin sensitivity, high estrogen receptor expression was detected. However, HTB-20, where tamoxifen did not enhance doxorubicin action, was also estrogen receptor positive. None of the cell lines had multidrug resistance related drug efflux and drug retention was not increased by the treatment with tamoxifen and verapamil. Cell cycle traverses were not altered by incubation with tamoxifen, verapamil or combinations thereof. These observatlons suggest mechanism of non-cytotoxic concentrations of tamoxifen and verapamil on doxorubicin cytotoxicity may involve one or more other cellular processes besides those of interference of estrogen binding to its receptor, cell cycle perturbation, or drug efflux blocking.

• Journal of Pharmaceutical Investigation
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• v.40 no.5
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• pp.269-275
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• 2010

P-gp plays a critical role in drug disposition and represents a mechanism for the development of multidrug resistance. Flavonoids, a major class of natural compounds widely present in foods and herbal products, have been shown to inhibit P-gp. Therefore, the aim of this study was to identify new candidate chemosensitizers by screening various plant extracts. The ability of natural plant extracts to inhibit P-gp activity was assessed by measuring cellular accumulation of calcein AM, daunorubicin and vincristine in P-gp overexpressing MDCKII-MDR1 cells. Among more than 800 plant extracts, eight were found to inhibit P-gp activity. Curcuma aromatica extract produced greatest inhibition, followed by Curcuma longa and Dalbergia odorifera extracts. Extracts of Aloe ferox, Curcuma zedoariae rhizome, Zanthoxylum planispinum, and Ageratum conyzoides showed moderate inhibitory effects. Curcumin and quercetin exhibited similar inhibition of P-gpmediated efflux of daunorubicin and vincristine, and flavones had a lesser effect. When chemosensitizing effect was evaluated by measuring daunorubicin sensitivity to MDCKII-MDR1 cells in the presence of natural plant extracts, Curcuma aromatica showed the most potent chemosensitizing effect based on daunorubicin cytotoxicity. In conclusion, natural plant extracts such as Curcuma aromatica can potently inhibit P-gp activity and may have potential as a novel chemosensitizers.

• Parasites, Hosts and Diseases
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• v.52 no.1
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• pp.105-109
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• 2014

Plasmodium falciparum malaria is a major public health problem in Thailand due to the emergence of multidrug resistance. The understanding of genetic diversity of malaria parasites is essential for developing effective drugs and vaccines. The genetic diversity of the merozoite surface protein-1 (PfMSP-1) and merozoite surface protein-2 (PfMSP-2) genes was investigated in a total of 145 P. falciparum isolates collected from Mae Sot District, Tak Province, Thailand during 3 different periods (1997-1999, 2005-2007, and 2009-2010). Analysis of genetic polymorphisms was performed to track the evolution of genetic change of P. falciparum using PCR. Both individual genes and their combination patterns showed marked genetic diversity during the 3 study periods. The results strongly support that P. falciparum isolates in Thailand are markedly diverse and patterns changed with time. These 2 polymorphic genes could be used as molecular markers to detect multiple clone infections and differentiate recrudescence from reinfection in P. falciparum isolates in Thailand.

• Korean Journal of Veterinary Service
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• v.37 no.1
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• pp.35-43
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• 2014

Salmonellosis has caused heavy losses in swine industry and implications for public health. Recently, the urgent problem of antibiotic resistance due to multidrug-resistant Salmonella spp. has been on the rise. The use of host-specific bateriophages as a biocontrol is one possible alternative. In this study, clinical signs, growth performance, quantification and detection of antigen, histopathological changes of gastrointestinal tracts were analyzed comparatively in weaned piglets according to administration of bacteriophages and challenge with Salmonella (S.) Typhimurium. Piglets challenged with S. Typhimurium after administered with bacteriophages showed reduced clinical signs, higher growth performance, lower bacterial shedding, lower quantificational value of antigens in intestines, higher V/C ratio and higher the number of goblet cells in intestines than piglets administered without bacteriophage and challenged with S. Typhimurium. These results indicate that feeding contained with bacteriophages has effect to prevent infection of S. Typhimurium in weaned piglets and suggest that a use of bacteriophage can be considered a valid antibiotic alternative.

• Bulletin of the Korean Chemical Society
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• v.32 no.10
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• pp.3666-3674
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• 2011

Overexpression of P-glycoprotein (Pgp) is associated with multidrug resistance (MDR) of tumor cells to a number of chemotherapeutic drugs. Pgp inhibitors have been shown to effectively reverse Pgp-mediated MDR. We prepared a series of phenoxy-N-phenylacetamide derivatives and tested for their ability to inhibit Pgp as potential MDR reversing agents, using a Pgp over-expressing MCF-7/ADR cell line. Some of the synthesized compounds exhibited moderate to potent reversal activity. Of note, compound 4o showed a 3.0-fold increased inhibition compared with verapamil, a well-known Pgp inhibitor. In addition, co-treatment of the representative compound 4o and a substrate anticancer agent doxorubicin resulted in a remarkable increase in doxorubicin's antitumor effect and inhibition of DNA synthesis in the MCF-7/ADR cell line. Taken together, these findings suggest that compound 4o could be a useful lead for development of a novel Pgp inhibitor for treatment of MDR.

• Journal of Korean Academy of Fundamentals of Nursing
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• v.22 no.3
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• pp.268-276
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• 2015

Purpose: The purpose of this study was to identify factors which influence the management of MultiDrug -Resistant Organisms (MDROs) by nurses in Intensive Care Units (ICUs). Methods: Data were collected from December 8 to 20, 2013 and participants were 163 ICU nurses working in one general hospital. The Health Belief Model tool and knowledge and management of MDROs infection tools were used in the study. Descriptive statistics, t-test, analysis of variances, Pearson correlation coefficients and multiple regression were used to analyze the data. Results: Knowledge, perceived susceptibility, and perceived benefits had a significant influence on MRSA (Methicillin Resistant Staphylococcus Aureus,) and MDRAB (Multidrug Resistant Acinetobacter Baumannii) infection management when all the other variables were considered. Significant variable which had influence on VRE (Vancomycin Resistant Eenterococci) infection management were perceived susceptibility and perceived benefits. Conclusion: Perceived susceptibility and perceived benefits had significant influence on MDROs infection management. Emphasis needs to be on the perceived susceptibility and perceived benefits of MDROs infection management when providing an educational program for ICU nurses.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2003.04a
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• pp.102-102
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• 2003

The present study has been undertaken to characterize availability of camellia(Camellia japonica L.) as a medicinal plant with antineoplastic and chemosensitizing activities. The crude extracts from fresn camellia flower, young leaves and nutraceutical tea of camellia leaf and flower buds were evaluated on their potential activities against various human cancer cells and multidrug resistance to cancer cells in vitro. The range of cytotoxicity displayed from 120$\mu\textrm{g}$/mL to 200$\mu\textrm{g}$/mL. Catemix 1(CT-1) mixed with camellia and green tea showed high toxicity(respectively IC$\sub$50/=l16$\mu\textrm{g}$/mL, 129$\mu\textrm{g}$/mL) against AML-2/WT, acute myelogenous leukemia cell and MCF-7, brest adenocarcinoma pleual effusion cell. Generally camellia tea mixed with green tea showed higher cytotoxicity than the other camellia teas mixed with some herbs(CH). Methanol extract of steamed camellia tea and roasted camellia tea had a chemosensitizing effect to reverse Pgp-mediated MDR. In addition, camellia flower tea of insignificant cytotoxicity, chemosensitizing effect were increased remarkably chemosensitizing effect in mixed flower tea with some herbs.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2004.05a
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• pp.27-29
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• 2004

Drug transporters play an essential role in the absorption, distribution and elimination of clinical drugs, nutrients and toxicants. The importance of the transporters is exampled by therapeutic failure in cancer chemotherapy that is mainly caused by the overexpression of multidrug resistance (MDR)-related transporters. In addition, the transporters may involve in drug-drug interactions that lead to serious adverse drug responses and some transporters also contribute to inter-individual variation in drug responses. As an effort to understand the mechanism underlying the inter-individual variation of transporters activity, genetic and environmental factors influencing the expression or function of the transporters have extensively explored through last decade. Among them, genetic polymorphism of drug transporter encoding genes has generated much interest since the discovery of functional single nucleotide polymorphisms (SNP) of MDR1 gene. Besides drug transporters, xenobiotic receptors also modulate drug disposition by regulating the transcription of drug metabolizing enzymes and drug transporters. Among many xenobiotic receptors, pregnane X receptor (PXR) and constitutive androstane receptor (CAR) are two most well characterized since these receptors show wide substrate specificities and regulate the expression of various enzymes involved in drug disposition. Recently, several functional genetic polymorphisms were reported in PXR coding gene. In the present study, genetic polymorphisms of two drug transporters, MDR1 and BCRP, and two xenobiotic receptors, PXR and CAR, were investigated in Korean population.