5, 8-Quinolinedione 유도체합성과 항진균 작용 연구

Abstract

5,8-Quinolinedione 유도체의 항진균작용을 측정하기 위하여 6-(N-arylamino) -7-chloro-5,8-quinolinedione유도체를 합성했다. 더불어 항균작용과 항암작용도 검색했다. 6,7-dichloro-5,8-quinolinedione은 5-amino-8-hydroxyquinoline을 HCI과 KC10_(3)로 산화하여 얻었다. ethano1을 용매로 CeCl_(3)존재하에서 6-(N-arylamino)-7-chloro-5,8-quinolinedione의 6번 위치로 aryl amine의 선택적 치환 반응을 시켜 80∼95%의 높은 수득률을 얻었다. 이들 유도체들은 Condida albicans ATCC 10231, 강남 성심병원의 환자로 부터 분리한 Candida albicans, Aspergillus niger KCTC 1231, Tricophyton mentagrophytes KCTC 6085와 같은 균에 대해 항진균작용을 검색하고 Bacillus subtilis ATCC 6633. Staphylococcus aureus ATCC 6538, Escherichia coli ATCC 10356, Pseudomonas aeruginosa NCTC 10490, methicillin resistant Staphylococcus aureus와 같은 균에 대해 항균작용을 검색했다. 그리고 rat의 leukemia cell인 P388D_(l)에 대하여 항암 작용을 검색했다. MIC값은 2배 희석 고체 배지법(twofold agar dilution method)에 의해서, 항암력은 MTT assay를 이용하여 측정했다. 새로이 얻은 유도체 가운데 6-(N-arylamino)-7-chloro-5,8-quinolinedione 6위치에 4-fluoroaniline, 3,4-difluoroaniline, 4-bromoani1ine, 3,4-dichloroaniline, 2,4-dibromoaniline, 3-chloro-4-methylaniline, 3-amino-acetophenon과 같은 aryl amino이 치환된 유도체(Y3, Y4, Y7, Y11, Y13, Y15, Y21)가 in vitro에서 우수한 항진균, 항균, 항암작용을 보였다.;In order to evaluate the antifungal, antibacterial, anticancer effect of 5,8-quinolinedione derivatives, we newly synthesized several 6-(N-arylamino)-7-chloro-5,8-quinolinedione derivatives. 6,7-Dichloro-5,8-quinolinediones were prepared by treating 5-amino-8-hydroxyquinoline with KClO_(3) in HCI. Substitution of 6,7-dichloro-5,8-quinolinedione with aryl amines in ethanol gave a6-(N-arylamino)-7-chloro-5,8-quinolinedions with 80∼95% yield. These derivatives were subjected to antibacterial and antifungal activity test, in vitro, against Candida albicans ATCC 10231, Candida albicans Local, Aspergillus niger KCTC 1231, Tricophyton mentagrophytes KCTC 6085, Bacillus subt ilis ATCC 6633, Staphylococcus aureus ATCC 6538, Escherichia coli ATCC 10356, Pseudomonas aeruginosa NCTC 10490, methicillin resistant Staphylococcus aureus. The MIC was determined by the two-fold agar/streak dilution method. The anticancer activities were determined by MTT assay, using leukemiacell. P388D_(1). Newly obtained some 6-(N-arylamino)-7-chloro-5,8-quinolinedione derivatives showed good anti fungal, antibacterial, anticancer activities in vitro. Among these derivatives, derivatives such as Y3, Y4, Y7, Y9, Yl3, Yl4, Y2O, Y2l showed more potent antifungal activities than fluconazole, ketoconazole, griseofulvin. Also most of derivatives had the antibacterial activities against Gram-positive bacteria. The cytotoxic effect against leukemia P388D_(1) cells of these derivatives showed that Y3, YS, Y18 had the percent survival of 13-15%.