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제강훈,Ki-Nam Kim,남궁우,조명행,Woongchon Mar 대한약학회 2005 Archives of Pharmacal Research Vol.28 No.3
Endosulfan is one of the organochlorine pesticides, which are well-known endocrine disruptors (EDs), and it acts as an estrogen agonist. Estrogen is a group of hormones that play an important role in mammary gland function and are implicated in mammary carcinogenesis. In the present study, we studied the effects of endosulfan on nodule like alveolar lesion (NLAL) formation in mouse mammary gland development using a mouse mammary gland organ culture (MMOC) system. Although endosulfan-treated mammary glands did not form NLALs, more alveolar buds were formed in this group than in the negative control (vehicle-treated) group. In addition, telomerase reverse transcriptase (TERT) mRNA expression levels were increased in endosulfan-treated mammary glands in a dose-dependent manner. Telomerase can be activated by estrogen, therefore, we examined the effects of endosulfan on telomerase activity, and found that the telomerase activity in estrogen receptor-positive MCF-7 cells was up-regulated by endosulfan treatment. Moreover, this activation was accompanied by the upregulation of the TERT mRNA expression. Also, transient expression assays using CAT reporter plasmids containing various fragments of the TERT promoter showed that this imperfect palindromic estrogen-responsive element is almost certainly responsible for the transcriptional activation by endosulfan. These results may help elucidate the endocrine disrupting mechanism of endosulfan.
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제강훈,한아름,이현태,Woongchon Mar,서은경 대한약학회 2004 Archives of Pharmacal Research Vol.27 No.1
A sesquiterpene lactone, 1-O-acetyl-4R,6S-britannilactone (1) isolated from the flowers of Inula britannica L. var. chinensis (Rupr.) Reg. (Compositae), was found as an iNOS inhibitory constituent for the first time with an IC50 value of 22.1 mM which is more potent than the positive control, L-N6-(1-iminoethyl)lysine (IC50 = 33.7 mM). Structure of compound 1 was identified by 1D and 2D NMR experiments and by comparison with the reference standard.
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DNA minor groove에 결합하는 tallimustine (FCE 24517)의 DNA 염기서열 특이성 결합
제강훈,이종순 嶺南大學校 基礎科學 硏究所 1998 基礎科學硏究 Vol.18 No.-
Tallimustine (FCE 24517) is an alkylating benzoyl mustard derivative of distamycin A. The antibiotic distamycin A is DNA minor groove binding agent that recognizes a stretch of at least four ATs. Tallimustine, like distamycin A, is expected to bind preferentially to AT-rich sequences in the minor grove of B-DNA. In this study we have determined covalent binding sites of tallimustine using heat-induced strand cleavage assay. The result shows that tallimustine alkylates alkylates the N3 adenine in the sequences ??(underline indicates the alkylation sites). In spite of the presence of a benzoyl nitrogen mustard group this compound fails to alkylate the N7 position of guanine, the major site of alkylation by conventional nitrogen mustards. It is clear that the alkylated adenine N3 is found only in the hexamer ?? sequences, suggesting that tallimustine has high base and sequence specificities in the minor groove of DNA.
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Je, Gang-Hoon,Son, Jong-Keun,O'Connor, Timothy R.,Lee, Jong-Soon 영남대학교 약품개발연구소 1999 영남대학교 약품개발연구소 연구업적집 Vol.9 No.-
A variety of alkylated base adducts are repaired by 3-methyladenine DNA glycosylases, one of the base excision repair enzymes. In this study, we examined the DNA adducts induced by hepsulfam and determined whether alkylated base adducts can be substrates for bacterial and msmmalian 3-methyladenine DNA glycosylases by electrophoresis methods. Hepsulfam, a synthetic analogue of busulfan, is known to alkylate DNA and form interstrand cross-links. The extent of DNA interstrand cross-links induced by hepsulfam and busulfan was found to be similar but significantly lower than that induced by chlorambucil, as measured by an agarose gel assay. The major monofunctional alkylation site of hepsulfam was observed at the N7 position of guanine, and not at the N3 position of adenine. Both compounds did not exhibit any sequence selective DNA alkylation patterns. The excision of hepsulfam-induced DNA adducts has been determined by treatment with homogeneous recombinant bacterial, rat and human 3-methyladenine DNA glycosylases and successive treatments by formamidopyrimidine-DNA glycosylase. The Escherichia coli alkA protein was shown to completely excise N7 guanine adducts, whereas mammalian 3-methyladenine DNA glycosylase failed to excise them. In addition, the cytotoxicity assay showed that E. coli mutant s1rains defective in the alkA gene or the uvrA gene were more sensitive to killing by hepsulfam than the wild type.
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남궁우,제강훈,Young-Jun Shin,강삼식,Woongchon Mar 대한약학회 2005 Archives of Pharmacal Research Vol.28 No.6
Eight furoquinoline alkaloids were purified from two plants belonging to the Rutaceae family. Kokusaginine, skimmianine, evolitrine, and confusameline were purified from Melicope confusa, and haplopine, robustine, dictamine, and γ-fagarine from Dictamnus albus. In this study, the eight furoquinoline alkaloids were examined for inhibitory potency against human phosphodiesterase 5 (hPDE5A) in vitro. DNA encoding the catalytic domain of human PDE5A was amplified from the mRNA of T24 cells by RT-PCR and was fused to GST in an expression vector. GST-tagged PDE5A was then purified by glutathione affinity chromatography and used in inhibition assays. Of the eight alkaloids, γ-fagarine was the most potent inhibitor of PDE5A, and its single methoxy group at the C-8 position was shown to be critical for inhibitory activity. These results clearly illustrate the relationship between PDE5A inhibition and the methoxy group position in furoquinoline alkaloids.
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Cytotoxic Compounds from the Roots of Juglans mandehurica
Kim, Sang-Hyun,Lee, Kyoung-Sun,Son, Jong-Keun,Je, Gang-Hoon,Lee, Jong-Soon,Lee, Chul-Hyun,Cheong, Chae-Joon 영남대학교 약품개발연구소 1998 영남대학교 약품개발연구소 연구업적집 Vol.8 No.-
Three new compounds, a diarylheptanone glucoside (1), 4, 5, 8-trihydroxy-α-tetralone 5-O-β-_(D)-[6'-O-(3", 5"-dimethoxy-4"-hydroxybenzoyl)]glucopyranoside (2), and 1, 4, 8-trihydroxy-3-naphthalenecarboxylic acid 1-O-β-_(D)-glucopyranoside methyl ester (3), were isolated from the roots of Juglans mandshurica, and their structures were elucidated on the basis of spectroscopic studies including 2D-NMR.
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