항암성 백금착체의 연구와 개발

黃圭子 숙명여자대학교 약학연구소 1999 약학논문집-숙명여자대학교 Vol.16 No.-

Since the discovery of antitumor activity of cisplatin by Rogenberg in 1969, various Pt complexes were prepared in order to decrease toxicity and to increase water-solubility. Carboplatin has good water-solubility and low nephrotoxicity as a 2nd generation antitumor agent. But it has narrow antitumor spectrum and cross-cisplatin resistance. Other various platinum complexes were synthesized, with an aim to have high and specific antitumor activity without or least toxicity. The interaction of Pt complexes with DNA have been found to mainly intrastrand crosslinking at N-7 of guanine base. Demonstration of correlation between anticancer drugs and the cell cycle may be useful in chemotherapeutic design. In the future, development of platinum complexes must be focused overcoming of limited antitumor spectrum, cisplatin-resistant cell inhibition and less toxicity.

鹽化알루미늄·高分子콤플렉스의 形態와 에스테르化反應 觸媒로서의 效果에 關한 硏究

黃圭子 淑明女子大學校 1978 論文集 Vol.18 No.-

Aluminum chloride·styrene-divinylbenzene copolymer complex have been prepared by the reaction of anhydrous aluminum chloride with styrene·divinylbenzene copolymer bead in the carbon disulfide solvent. The shape of aluminum chloride·styrene-divinylbenzene copolymer complex have been studied by the use of optical microscope, stereomicroscope, scanning electron microscope and analysis of atomic absorption and electron microprobe X-ray. The catalytic effect of aluminum chloride·styrene-divinylbenzene copolymer complex in the process of esterification of various organic acids such as acetic acid, n-butyric acid, iso-valeric acid, cyclohexane carboxylic acid, benzoic acid, p-hydroxy benzoic acid and phthalic acid etc., with several aliphatic and aromatic alcohols have been studied. Thus, diethyl esters of aliphatic dibasic acid such as malonic acid were synthesized and their relationships with chemical and stereochemical structure were investigated. The results were summarized as follows: 1. Aluminum chloride·styrene-divinylbenzene copolymer complex could be prepared from the styrene·divinylbenzene copolymer and anhydrous aluminum chloride. 2. The aluminum content increased with the increase of reaction time and the decrease in size of polymer particle. 3. The yield of esterification of organic acid and alcohol increased with use of aluminum chloride·styrene-divinylbenzene copolymer complex as catalyst and it was influenced by the chemical structure of organic acid and alcohol. 4. Stereochemical specificity could be observed in the esterification of geometrical isomer such as maleic acid when the reaction was conducted using aluminum chloride· styrene-divinylbenzene copolymer complex as catalyst.

새로운 백금착체의 설계와 그 항암활성

황규자,이근임,권영이 숙명여자대학교 약학연구소 1996 약학논문집-숙명여자대학교 Vol.12 No.-

Pt(Ⅱ) and Pt(Ⅳ) complexes having six-membered chelate rings with N,N'-bis(2-chloroethyl)propanediamine (2-CePn) as carrier ligand have been prepared and characterized by IR and ^1H NMR. These complexes were examined for their in vitro cytotoxicity against leukemia L1210 and P388 cell lines. The cytotoxicity of platinum complexes with 1,3-propanediamine were improved by introduction of 2-chloroethyl group which nitrogen mustard, and alkylating agent, contains. The Pt(Ⅱ) complex showed more effective cytotoxicity than Pt(Ⅳ) complex.

리보플라빈을 가진 수용성 백금(Ⅱ)착체의 합성과 항암활성 및 세포주기와의 관계

황규자,권영이 숙명여자대학교 약학연구소 1999 약학논문집-숙명여자대학교 Vol.16 No.-

A series of vitamine-containing Pt(II) complexes of the type [Pt(Rf)(L)], (where Rf=riboflavin, L=ethylenediamine, 1,3-propanediamine, 1,4-butanediamine) was synthesized and characterized by IR, electronic absorption, elemental analysis and FAB-Mass. The coordination sites of Rf to Pt(II) ions were determined to be N(5) and 0(6) with resultant chelate ring formation. These compouds have much better water solubility(145- 150mg/ml) than cisplatin has(lmg/ml). The anticancer activity of this Riboflavin-containing Pt(II) series was investigated by MTT assay against mouse and human leukemia cell lines in vitro. Interaction between Pt(II) complex and DNA were analyzed by flowcytometry, and showed G2/M arrest in LI210 cell line.

7원환 구조를 갖는 새로운 백금착체의 합성에 대한 연구

황규자,권영이 숙명여자대학교 약학연구소 1998 약학논문집-숙명여자대학교 Vol.14 No.-

Platinum complexes having 7 .membered ring structure with Riboflavin(RF) and Flavin mononucleotide(FMN) as leaving group were synthesized to enhance antitumor activity and solubility. Platinum complexes with RF and FMN were determined by ir spectra, nmr spectra, mass and elemental analysis.

카르복스아닐리드와 티오카바메이트의 합성 및 그 항바이러스 활성

황규자,이희경 숙명여자대학교 약학연구소 1997 약학논문집-숙명여자대학교 Vol.13 No.-

New carboxanilides and thiocarbamalGS w&i'e designed and synthesized basod on the structure- activity relationship for ihe purpose of the developement of lead compound effective in reverse trariseriptase of HIV viruses, Seven kinds of tiie carboxanilides of which dihydrooxatbiin moiety of known dihydroox&thiin was substituted to now heterocyclic group and seventeen kinds of new thioc^fbarnates were synthesized through modification of tlio phenyl group in the structures. Syntheses include either the substitution of sulfur and oxygen in dibydrooxatbiin each other or nitrogen, or introduction of another double bond in the heterocyclic ring by (he Piunmerer reaction. In the synthesis of the thiocarbamatefc deriva lives, new substituents in phenyl group or htrteroaryl were introduced. Reaction of alkyl alcohol tbiophosgen and aryl amine gave &lkyl thiocarbamate in tetrabydrduran in high yield without isolation of intermediate. Screening for antiviral activity of the synthesized now compounds against the typical three kinds of viruses HSV-1, VSVf HIV-1) were carried oul The thiocarbarciate 35 with which a chlorine on mete and a methyl on parin phenyl group showed a good result in lotficity and selectivity in the screening. Tba wrboaaniiide 25 showed a moderate activity in comparison with UC84 and UC38.

Ethylenediamine類를 배위자로 하는 백금착체의 항암활성과 그 신장독성에 관한 연구(Ⅲ)

黃圭子,李根姙 숙명여자대학교 약학연구소 1993 약학논문집-숙명여자대학교 Vol.9 No.-

Several Pt( D ) and Pt(IV) complexes of N,N'-bis(2-hydroxyethyl) ethylenediamine(2-HEen) and N,N*-bis(2-chloroethyl) ethylenediamine (2-CEen) as carrier ligand were prepared. Water-soluble Pt complexes were also prepared by modification of leaving groups. The cytotoxicity of these compounds against leukemia P388 in vitro were tested. The Pt complexes containing 2-CEen showed higher antitumor activity than those containing 2-HEen. Through the nephrotoxicity tests on the primary cultured proximal tubular cells of rabbit kidney and human kidney cells in vitro, Pt complexes with 2-CEen showed higher than those with 2-HEen which were consistent with cytotoxicity but showed very low nephrotoxicity compared with cisplatin. Also the valus of BUN and creatinine in serum of Pt complexes were reduced remarkably compared with cisplatin, therefore it can be concluded that new Pt complexes seems to have much lower nephrotoxicity than cisplatin.

에폭시드 고리 개환에 의한 옥사졸리딘티온의 합성 및 항바이러스 활성

황규자,이희경,한호규 숙명여자대학교 약학연구소 1998 약학논문집-숙명여자대학교 Vol.15 No.-

A synthesis and antiviral actvity of new oxazolidinthiones are discribed. Based on the structure-activity relationship from UC38 and UC84, 4-chloro-3-isopropyloxycarbonylphenylamino moiety is found to be a essential pharmacophore for activity. The oxazolidines, which are cyclic thiocarbamate of a 5-membered ring were designed by molecular modification of UC38. Nucleophilic attack of substituted aniline to epoxide by using lithiumperchlorate as a catalyst gave 2-aminoalcohols in good yields. Treatment of 2-aminoalcohol either with thiophosgen or with thionyl chloride gave oxazolidinthiones and 5-chloromethyl-N-phenyl-1,2,3-oxathiazolidin-2-oxide, respectively. Screening results of the 8 oxazolidinthiones against the typical three kinds of viruses(HSV-l, VSV, HIV-1) showed lower activity than those of the UC84 and UC38.

Peutz-Jeghers 증후군 1예

최규식,황영남,김영자,양윤모,최영호 대한가정의학회 1985 Korean Journal of Family Medicine Vol.6 No.12

한국의 발톱진균증 환자의 삶의 질에 관한 연구

조백기,박종갑,김형옥,김성욱,백승철,김진우,김시용,안규중,전재복,오지원,김낙인,이규석,오칠환,김수남,김상태,손숙자,신용우,김동석,이원우,권경술,서대헌,황규왕,이종석,고재경,강원형,정기양,최응호,김기홍,박석돈,강승주,함정희,명기범,김방순,구상완,김병수,원영호,김한욱,송은섭,정병수,노병인,홍창권,박장규,한지윤,김광중,구대원,김종민,김재홍,유희준,양경미 대한의진균학회 1998 대한의진균학회지 Vol.3 No.2

Background: Onychomycosis, especially toenail onychomycosis has become one of the common fungal infection and has historically been regarded as a cosmetic rather than medical problem by many patients, even by physicians. Recently, however, there are several reports that is a refractory disease which may cause a deleterious effect on patiets quality of life (QOL). Objective: The purpose of this study was to investigate the impact of toenail onychomycosis on QOL in Korea and to assess the chandes of QOL after treatment. Methods: Total 1004 patients with toenail onychomycosis which was confirmed by clinical findings and KOH preparation were were enrolled at 47 dermatologic centers in Korea, and interviewed with standardized QOL questionnaire before and after sytemic antifungal treatment. Responses to the questionnaire were scored by 5-point scale (1∼4) and averaged, and were analyzed for 5 dimensions of emotional impact, social impact, symptorn and functional impact, patients views concerning treatment, and relationship with doctor. Results: 1. Before and after treatment, the most serious impact was emotional dimension showing 1.90 and 1.30 in average score (AS), and social (AS: 1.14 and 0.83) and symptom and functional impact (AS: 1.05 and 0.92) was also affected. 2. In female rather than male, statistically more significant impact on patients QOL was observed in all dimensions. 3. After treatment, 3 of 5 dimensions were improved significantly - emotional dimension (AS : from 1.90 to 1.30), social dimension (AS: from 1.14 to 0.83), patients view concerning treatment (AS: from 1.34 to 1.02). 4. The drgree of patients satisfaction at the therapeutic effect was very high- 62.4% (immediately after treatment) and 65.8% (9 months affer initiation of treatment) of patients answered excellent or good. Conclusion: This study confirms that toenail onychomycosis has significant impact on the overall QOL of patients. Also the effect of antifungal therapy on patients QOL were watisfactory. Therefore, both doctor and patient should pay more attention to the treatment of onychomycosis. [Kor J Med Mycol 3(1): 115∼124]