新型苯并咪唑桥接Aren钌矩形在人乳腺癌细胞中的抗菌和抗增殖活性

Ersin Orhan, Görkem Dülger, M. Alpay, Nilüfer Öksüz, B. Dülger
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引用次数: 0

摘要

从相应的双核芳烃钌化合物[Ru2(对花香烃)2(µ4-OOᴖOO)}2(µ4-bbim)] (OOᴖOO = 2,5-二氧基-1,4-苯并喹啉(dobq), 2,5-二氯-1,4-苯并喹啉(dClbq), 2,5-二溴-1,4-苯并喹啉(dBrbq), 2,5-二溴-1,4-苯并喹啉(dBrbq),草酸(oxa),5,8-二氧基-1,4-萘醌(donq)与bbim分子和AgCF3SO3反应。四核芳烃钌化合物对人乳腺癌细胞株(MDA-231-MB)的抗增殖活性进行了评价,化合物2在给药24和48 h时的抗增殖作用最强。此外,其他化合物均表现出良好的癌细胞选择性和极低的微摩尔细胞毒性。并对合成的化合物进行了抑菌活性测定。抗10种细菌(如大肠杆菌ATCC10536、金黄色葡萄球菌ATCC 6538P、表皮葡萄球菌ATCC 12228、肺炎克雷伯菌UC57、普通变形杆菌ATCC 8427、金黄色假单胞菌ATCC 27853、粪肠球菌ATCC 29212、弗氏柠檬酸杆菌ATCC 8090、污物分枝杆菌CCM 2067和单核细胞增生李斯特菌ATCC 15313)和7种酵母培养物(如光秃假丝酵母ATCC 90030、热带假丝酵母ATCC 13803、白色假丝酵母ATCC 10231、脆弱克卢维菌属nrrl2415,红红酵母属DSM 70403,汉氏德巴雷菌属DSM 70238,吉勒蒙氏汉氏菌属DSM 3432)。采用纸片扩散法和最低抑菌浓度(MIC)稀释法。特别是,化合物对革兰氏阴性菌的抑菌作用优于革兰氏阳性菌,对念珠菌的抑菌作用更强。结果表明,苯并咪唑桥接的钌矩形化合物是非常强效的缓蚀剂。
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Antimicrobial and Antiproliferative Activities of New Benzimidazole-Bridged Aren Ruthenium Rectangles in Human Breast Cancer Cells
Some novel the benzimidazole-bridged aren ruthenium rectangles compounds of the general structure [{Ru2(p-cymene)2(µ4-OOᴖOO)}2(µ4-bbim)]4+ (bbim = 1,1'-butyl-2-ene-di(benzimidazole) were obtained from the corresponding double nuclear arene ruthenium compounds [Ru2(p-cymene)2(µ4-OOᴖOO)Cl2] (OOᴖOO = 2,5-dioxido-1,4-benzoquinonato (dobq),  2,5-dichloro-1,4-benzoquinonato (dClbq),  2,5-dibromo-1,4-benzoquinonato (dBrbq), oxalato (oxa), 5,8-dioxido-1,4-naphtoquinonato (donq) by reaction with the bbim molecule and AgCF3SO3. The antiproliferative activity of the tetranuclear arene ruthenium compounds was evaluated on their anti-cancer properties against human breast cancer cell line (MDA-231-MB), compound 2 showed the highest antiproliferative effect among the other compounds during 24 and 48 hours administration. Also, other all compounds showed very good cancer cell selectivity and very low micromolar cytotoxicities. In addition, antimicrobial activities of the synthesized compounds were determined. Against ten bacteria (such as Escherichia coli ATCC10536, Staphylococcus aureus ATCC 6538P, Staphylococcus epidermidis ATCC 12228, Klebsiella pneumoniae UC57, Proteus vulgaris ATCC 8427, Pseudomonas aureginosa ATCC 27853, Enterococcus faecalis ATCC 29212, Citrobacter freundii ATCC 8090, Mycobacterium smagmatis CCM 2067 and Listeria monocytogenes ATCC 15313) and seven yeast cultures (such as Candida glabrata ATCC 90030, Candida tropicalis ATCC 13803, Candida albicans ATCC 10231, Kluyveromyces fragilis NRRL 2415, Rhodotorula rubra DSM 70403, Debaryomyces hanseni DSM 70238, Hanseniaspora guillermondii DSM 3432). Using the disk diffusion method as well as the minimal inhibitory concentration (MIC) dilution method. Especially, the compounds exhibit potential antibacterial effects against Gram negative bacteria than Gram positive bacteria and showed superior antifungal effect agaist candida species.  The results revealed that the benzimidazole-bridged aren ruthenium rectangles compounds were the very strong potent inhibitor.
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