Cihan-Üstündağ Gökçe, Naesens Lieve, Şatana Dilek, Erköse-Genç Gonca, Mataracı-Kara Emel, Çapan Gültaze
1Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Istanbul University, Istanbul, 34116 Turkey.
2Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, 3000 Louvain, Belgium.
Monatsh Chem. 2019;150(8):1533-1544. doi: 10.1007/s00706-019-02457-9. Epub 2019 Jul 17.
A series of indole-based spirothiazolidinones have been designed, synthesized and evaluated, in vitro, for their antitubercular, antiviral, antibacterial, and antifungal activities. The structures of the new compounds were established by IR, H NMR, C NMR (proton decoupled, APT, and DEPT), electrospray ionization mass spectrometry, and microanalysis. Compounds bearing a phenyl substituent at position 8 of the spiro ring, exhibited significant antitubercular activity against H37Rv ATCC 27294 at concentrations of 3.9 and 7.8 µM. Still, some of the tested compounds displayed activity on mycobacteria with MIC values of 16 and 31 µM. Four of the indole-spirothiazolidinone derivatives were found to be moderately active against Punta Toro virus, yellow fever virus or Sindbis virus in Vero cells. The antiviral EC values were in the range of 1.9-12 µM and the selectivity index (ratio of cytotoxic to antivirally effective concentration) was above 10 in some cases. The most potent effect was seen with the compound that is methylated at positions 2 and 8 of the spirothiazolidinone system.
设计、合成了一系列基于吲哚的螺噻唑烷酮，并对其抗结核、抗病毒、抗菌和抗真菌活性进行了体外评估。通过红外光谱、氢核磁共振、碳核磁共振（质子去耦、APT和DEPT）、电喷雾电离质谱和微量分析确定了新化合物的结构。在螺环8位带有苯基取代基的化合物，在浓度为3.9和7.8 μM时，对H37Rv ATCC 27294表现出显著的抗结核活性。不过，一些受试化合物对分枝杆菌也有活性，其最低抑菌浓度值为16和31 μM。发现四种吲哚-螺噻唑烷酮衍生物在Vero细胞中对蓬塔托罗病毒、黄热病毒或辛德毕斯病毒有中等活性。抗病毒半数有效浓度值在1.9 - 12 μM范围内，在某些情况下，选择性指数（细胞毒性与抗病毒有效浓度之比）高于10。在螺噻唑烷酮系统2位和8位甲基化的化合物表现出最显著的效果。
