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.

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.

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.

Burley와 황색종 잎담배들의 Toast과정 중 Pyrazine의 생성

명평근,김천석 충남대학교 약학대학 의약품개발연구소 1989 藥學論文集 Vol.5 No.-

The change of volatile flavoring components and the formation of pyrazine during toasting condition of Burley and Flue-cured tobacco leaves in the manufacturing process were analyzed by Gas Chromatograph. The results are as following: 1. After the toasting treatment of Burley 21 and Flue-cured tobacco leaves, the amounts of pyrazine and its derivatives, furfural and its derivatives, benzaldehyde, maltol, beta-Ionone and beta-Ionone epoxide were reduced, while the increasing components were hexanol, terpineol and neophytadiene. 2. The optimum condition of Burley 21 tobacco leaves on the toasting treatment was that the addition of sucrose was 4~7% and that of the formation of pyrazine was 125℃ for the treatment temperature and 5 minutes for the treatment time.

Basma 잎담배의 Vacuum Tobacco Conditioning (VTC)와 Compressed Tobacco Conditioning(CTC)처리에 따른 향기성분분석

명평근,김천석 충남대학교 약학대학 의약품개발연구소 1989 藥學論文集 Vol.5 No.-

Volatile flavors of Basma tobacco by Vacuum Tobacco Conditioning (VTC) and Compressed Tobacco Conditioning (CTC) treatments were analyzed by Gas Chromatogaphy. The Results obtained from this experiment are as following: 1. As Basma tobacco leaves were processed by VTC treatment, the amounts of volatile components of benzyl alcohol, phenyl acetaldehyde and dibutyl phthalate were reduced, while that of damascone was increased. 2. After CTC treatment the reduced volatile flavors of Basma tobacco leaves were benzyl alcohol, 7-undecane+Linalool, 2-phenylethyl alcohol, thymol, dibutyl phthalate, n-pentacosane and n-hexacosane, while the increasing components were furfural, phenyl acetate and n-eicosane. 3. In order to minimize the change of flavoring components of Basma tobacco leaves during the preconditioning, we should plan to improve the working method to minimize the heating and steam flow and to treat at the lower temperature and within short time.

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.

2D-QSAR and HQSAR of the Inhibition of Calcineurin-NFAT Signaling by Blocking Protein- Protein Interaction with N-(4-oxo-1(4H)-naphthalenylidene)benzenesulfonamide Analogues

명평근,Nack-Do Sung 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.8

The inhibition of calcineurin-NFAT signaling by blocking protein-protein interaction with N-(4- oxo-1(4H)-naphthalenylidene)benzenesulfonamide analogues was studied in order to obtain mechanistic information about the effects of structural modification and molecular design of immunomodulation agents. The study was carried out by quantitative structure-activity relationship (QSAR) analysis using 2D-QSAR and hologram QSAR (HQSAR) methods. The statistical results of the two models showed the best prediction and fitness (r2>0.900) for the inhibition activities. The inhibitory activities from the 2D-QSAR models were dependent upon the electronic affinity of electron acceptor and optimum dipole moment (DMopt.=4.491 Debye). In addition, the HQSAR model provided information about which structural distinctions could be significant contributors the inhibition.

향신료의 항산화 및 아세틸콜린에스터라제 저해작용

명평근,엄선섭 충남대학교 형질전환복제돼지연구센터 2004 논문집 Vol. No.8

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-propenyl)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.

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.