항암항생제 Mitomycin C와 DNA의 상호작용

양평근,김춘성,윤병태,이천배 忠南大學校 癌共同硏究所 1991 癌共同硏究所 硏究誌 Vol.1991 No.-

향신료의 항산화 및 아세틸콜린에스터라제 저해작용

명평근,엄선섭 충남대학교 약학대학 의약품개발연구소 2004 藥學論文集 Vol.19 No.-

Alzheimer's disease(AD) involves a chronic CNS inflammatory response that is associated with both head injury and beta-amyloid pathology. It was reported that the curry spice curcumin reduced oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. Methanol extracts of 18 spices were screened for inhibition of acetylcholinesterase and antioxdative activity in order to evaluate the antidementia activity. The results showed that DPPH radical scavenging activity(IC_(50)) of Origanus majorana, Salvia officinalis, and Pimenta dioicallis are 161, 179, 71 (㎍/㎖) respectively and the AChE inhibitor activity(% inhibition at 1 mg/㎖) were 53.8, 60.5, 54.6 %, respectively. Bioassay-guided fractionation of Pimenta dioicallis yielded 2-methoxy-4-(2-pro-penyl)phenol and 2-methoxy-4-(1-propenyl)phenol as antioixdative constituents. It suggest that Pimenta dioicallis(allspice) is a good source of antidementia agent for AD.

殺蟲性 O,O-Diethylphenylphosphate 誘導體들에 의한 Acetylcholinesterase의 Phosphorylation에 關한 量子藥理學的 硏究

明平根,成洛道,柳柄泰,李天培 충남대학교 약학대학 의약품개발연구소 1986 藥學論文集 Vol.2 No.-

Quantum pharmacological study has been carried out for the phosphorylation process of acetylcholinesterase (Ach E) and hydrolysis reaction of O,O-diethylphenylphosphate (DPP) derivatives. Quantum variables of DPp molecule were calculated by extended Hu¨ckel theory (EHT) molecular orbital calculation method and linear free energy relationship(LFER) parameters were applied to the Hamett, Taft & Swain-Luption's simple and dual substituents parameter equation. The results shows that the field effect (F) was larger than resonance effect (R) and the values of percent field (%F) and percent resonance (%R) were about %F=34 and %R=66, respectively, yielding the ratio of F to R of 2:1. From the regression analysis, the various quantum chemical parameters, the net charge of phosphorus atom and that of meta carbon atom, the LUMO energy and the electrophilic superdelocalizability were influenced significantly on the phosphorylation of Ach E. The charge-controlled and orbital-controlled reactions proceed via trigonal bypyramidal penta-coordinated intermediate with pseudorotation.

항암항생제 Mitomycin C와 DNA의 상호작용

명평근,김춘성,유병태,이천배 충남대학교 암연구소 1991 癌共同硏究所 硏究誌 Vol.1 No.1

Mitomycin C is a clinically used antitumor antibiotic that binds covalently to deoxyribonucleic under reductive or acidic catalysis. We have investigated the confirmation, the determination of thermal melting point(Tm), the inhibition of S1 nuclease and exonuclease I and the transformation of supercoiled closed circular(SCC) PBR 322 DNA on the Mitomycin C-DNA complex. It was identified that Mitomycin C was reduced by 0.001M HC1 (pH<4), 0.01M NaBH_(4) and ascorbic acid. The alkylation of DNA by Mitomycin C was increased Tm; The Tm of control λDNA was 77.25℃ whereas Tm of Mitomycin C-DNA complex was 80℃. It was founded that Mitomycin C-DNA complex inhibited the activity of the S1 nuclease and exonuclease III. The SCC pBR 322 DNA was transformed into more open circular (OC) form by increasing concentration of the Mitomycin C. It is suggested that the interaction of Mitomycin C with DNA effects the conformation of DNA.

토끼 귀의 출혈모델에서의 스트렙토키나제-덱스트란 포합체의 혈전용해효과 및 항원성 평가

명평근,최수라,박목순,박진규 충남대학교 약학대학 의약품개발연구소 2000 藥學論文集 Vol.16 No.-

The way in which a thrombolytic agent, streptokinase(SK, Dongkook) and streptokinase-Dextran conjugate(SK-DEX, Russia), cause the dissolution of haemostatic plugs of different ages was investigated in a novel rabbit bleeding model, and antigenicity of SK and SK-DEX was elvalutated by indirect ELISA using antisera collected after 7 days intravenous injection to a rabbit ear. Standardized incisions were made on rabbit ear and the wounds were left to heal for 0.5 h or 24 h, before the thrombolytic agent was infused. SK showed a pronounced fresh colt selectivity since it was significantly more effective in lysing flesh clots than old ones (96% vs 52%) respectively, percent lysis of haemostatic plus of different ages with SK-DEX conjugate (150,000 IU/㎏) was more effective in lysing fresh clots than old ones (20% vs 0%) respectively. The time onset of bleeding observed for SK(Dongkook) (19min) was the same as that of SK (Kabi) (19min), but the bleeding time observed for SK(Dongkook) (90 min) was twice longer than that formed SK(Kabi) (49min). However, the time to onset of bleeding of SK-DEX(Russia) (61min) was longer than that of the formed SK(Dongkook) (19 min). The bleeding time observed for SK-DEX(Russia, 150,000 IU/㎏) (1min) was shorter than that found for SK(Dongkook) (90min). The antigenicity of SK-DEX(Dongkook) was more effective than that of SK(Dongkook) in comparision with each control. These results suggest that the fresh clot selectivity demonstrated for SK and SK-DEX may be clinically beneficial and remains to be clarified by further invertigations.

항암항생제인 CC-1065 유사체들의 지연된 죽음과 DNA 염기서열특이성과의 상관성(I)

明平根 충남대학교 약학대학 의약품개발연구소 1988 藥學論文集 Vol.4 No.-

Subtle changes in analog structure sometimes lead to dramatic changes in biological activity. By examining how changes in CC-1065 structure effect DNA sequence specificity, and local DNA structure the author will search for correlations between these effects and biological endpoints such as delayed death, cytotoxic potency and antitumor efficacy. The results of these experiments will guide us in designing new CC-1065 analogs, and choosing select compounds and DNA sequences for further structural and biochemical studies. While (+)-CC-1065 and (+)-AB'C' produce delayed death in mice at less than therapeutic doses, (+)-ABC and (+)-ABC'' do not. Since (+)-CC-1065 and (+)-AB'C' have identical DNA sequence specificity, it is expected that compounds that mimic the inside edge substituents of these compounds might also produce delayed death in moce. In order to evaluate this proposal, the author has compared the sequence specificity of various different CC-1065 analogs in ^32P labeled restriction enzyme fragments from SV 40 DNA. Correlation between delayed death and DNA sequence specificity suggests that synthetic analogs which mimic concave edge substituents of (+)-CC-1065 might bind to certain DNA sequences, result in specific biochemical and biological consequences, which ultimately lead to delayed death in mice.

항암항생제인 CC-1065 유사체들의 지연된 죽음과 DNA 염기서열특이성과의 상관성(Ⅰ)

明平根 충남대학교부설 생명공학연구소 1991 생물공학연구지 Vol.1 No.-

Subtle changes in analog structure sometimes lead to dramatic changes in biological activity. By examining how changes in CC-1065 structure effect DNA sequence specificity, and local DNA structure the author will search for correlations between these effects and biological endpoints such as delayed death, cytotoxic potency and antitumor efficacy. The results of these experiments will guide us in designing new CC-1065 analogs, and choosing select compounds and DNA sequences for further structural and biochemical studies. While (+)-CC-1065 and (+)-AB′C′ produce delayed death in mice at less than therapeutic doses, (+)-ABC and (+)-ABC″ do not. Since (+)-CC-1065 and (+)-AB′C′ have identical DNA sequence specificity, it is expected that compounds that mimic the inside edge substituents of these compounds might also produce delayed death in mice. In order to evaluate this proposal, the author has compared the sequence specificity of various different CC-1065 analogs in ^32P labeled restriction enzyme fragments from SV 40 DNA. Correlation between delayed death and DNA sequence specificity suggests that synthetic analogs which mimic concave edge substituents of (+)-CC-1065 might bind to certain DNA sequences, result in specific biochemical and biological consequences, which ultimately lead to delayed death in mice.

Ethanol 수용액중에서 N-(2,3-xylyl)anthranilic Acid의 반응

明平根,成洛道,朴戊淳 순천향대학교 1982 논문집 Vol.5 No.1

Kinetics studies on the hydrolysis of N-(2,3-xylyl) anthranilic acid in 50% aqueous ethanol binary mixture have been carried out by means of ultraviolet spectrophotometry at 25℃. Analysising pH-rate profile, the rate constants consists of two parts; (1) pH independent part, (2) dependent on hydronium ion. Results of m-value of Grunwald-Winstein plot (m=0.3), n-value of Kivinen plot(n= 1.35), show that the solvolysis displacement of N-(2,3-xylyl)- anthranilic acid proceed via SN 2 type mechanism. And the dissociation constant of N-(2,3-xylyl) anthranilic acid in 50% aqueous ethanol solution twas measured by spectrophotometry method which value was ?? at 25℃. From the above results are hypothesized as following. That is, the hydrolysis proceed through SN 2 type mechanism below pH 3.50(pKa <[??]) and addition-elimination above PH 5.5(pKa>[??]) In the range of pH 3.5∼5.5, these two reactions occur competitively.

이종장기이식에 의한 면역거부반응에서 IL-18의 역할

명평근,최연실,심정현,김은미 충남대학교 생물공학연구소 2003 생물공학연구지 Vol.9 No.2

Although transplantation immunology as a distinctive field began with the development of experimental models that showed the feasibility of bone marrow transplantation (BMT), organ engraftment was accomplished first in humans, and was though for many years to occur by drastically different mechanism. The liver, skin, and gastrointestinal tract are major target organs of acute graft-versus-host disease (GVHD), the major complication of allogenic BMT. The pathophysiology of acute GVHD involves in the dysregulation of pro-inflammatory cytokine cascade and donor T-cell responses to host alloantigens. Interukine-18 (IL-18) was initially known as interferon-g-inducing factor with potent immunomodulatory effects. The level of IL-18 is increased in acute GVHD, but little has been known about its role in thepathophysiology of acute GVHD. It reduces the severity of acute GVHD as a Thl-inducing cytokine early after BMT to the lethally irradiated recipients. When administered to the donor, it can also reducing the severity of acute GVHD, as a Th2-inducing cytokine. Therefore, IL-18 has the remarkable capacity to modulate acute CVHD when administered either to the donor or the recipient through distinct mechanism. Here, we present our view of the concepts of transplantation immunology and the role of IL-18 in the graft rejection.

항암항생재 Mitomycin C와 DNA의 상호작용

명평근,김춘성,유병태,이천배 충남대학교 약학대학 의약품개발연구소 1990 藥學論文集 Vol.6 No.-

Mitomycin C is a clinically used antitumor antibiotic that binds covalently to deoxyribonucleic under reductive or acidic catalysis. We have investigated the confirmation, the determination of thermal melting point(Tm), the inhibition of S1 unclease and exonuclease Ⅲ and the transformation of supercoiled closed circular(SCC) PBR 322 DNA on the Mitomycin C-DNA complex. It was identified that Mitomycin C was reduced by 0.001M HCl pH<4), 0.01M NaBH_4 and ascorbic acid. The alkylation of DNA by Mitomycin C was increased Tm; The Tm of control λDNA was 77.25℃ whereas Tm of Mitomycin C-DNA complex was 80℃. It was founded that Mitomycin C-DNA complex inhibited the activity of the S1 nuclease and exonuclease Ⅲ. The SCC pBR 322 DNA was transformed into more open circular (OC) form by increasing concentration of the Mitomycin C. It is suggested that the interaction of Mitomycin C with DNA effects the conformation of DNA.