KiranKumar Hulihalli N, RohitKumar Heggodu G, Advirao Gopal M
Department of Biochemistry, Davangere University, Davangere, Karnataka, India.
Department of Biochemistry, Davangere University, Davangere, Karnataka, India.
J Photochem Photobiol B. 2018 Jan;178:1-9. doi: 10.1016/j.jphotobiol.2017.10.022. Epub 2017 Nov 1.
Two new derivatives of pyrimido[4',5';4,5]thieno(2,3-b)quinoline (PTQ), 9-hydroxy-4-(3-diethylaminopropylamino)pyrimido[4',5';4,5]thieno(2,3-b)quinoline (Hydroxy-DPTQ) and 8-methoxy-4-(3-diethylaminopropylamino)pyrimido[4',5';4,5]thieno(2,3-b)quinoline (Methoxy-DPTQ) were synthesized and their DNA binding ability was analyzed using spectroscopy (UV-visible, fluorescence and circular dichroism), ethidium bromide dye displacement assay, melting temperature (T) analysis and computational docking studies. The hypochromism in UV-visible spectrum and increased fluorescence emission of Hydroxy-DPTQ and Methoxy-DPTQ in the presence of DNA suggested the molecule-DNA interaction. The association constants calculated from UV-visible and spectral titrations were of the order 10 to 10M. Circular dichroism studies corroborated the induced conformational changes in DNA upon addition of molecules. The change in the ellipticity was observed both in negative and positive peak of DNA, thus, suggesting the intercalation of molecules. The observed displacement of ethidium bromide from the DNA and increased T, upon addition of DNA confirmed the intercalative mode of binding. This was further validated by computational docking, which showed clear intercalation of molecules into the d(GpC)-d(CpG) site of the receptor DNA. Anticancer activities of these molecules are evaluated by using MTT assay. Both molecules showed antiproliferative activity against all the three cancer cells studied, with Hydroxy-DPTQ being more potential molecule among the two. IC value of Hydroxy-DPTQ and Methoxy-DPTQ were in the range of 3-5μM and 130-250μM, respectively.
合成了嘧啶并[4',5';4,5]噻吩并(2,3 - b)喹啉(PTQ)的两种新衍生物，即9 - 羟基 - 4 - (3 - 二乙氨基丙基氨基)嘧啶并[4',5';4,5]噻吩并(2,3 - b)喹啉(羟基 - DPTQ)和8 - 甲氧基 - 4 - (3 - 二乙氨基丙基氨基)嘧啶并[4',5';4,5]噻吩并(2,3 - b)喹啉(甲氧基 - DPTQ)，并使用光谱法(紫外可见光谱、荧光光谱和圆二色光谱)、溴化乙锭染料置换试验、熔解温度(Tm)分析和计算对接研究分析了它们与DNA的结合能力。在DNA存在下，羟基 - DPTQ和甲氧基 - DPTQ的紫外可见光谱中的减色现象以及荧光发射增强表明了分子与DNA的相互作用。由紫外可见光谱和光谱滴定计算得到的缔合常数在10⁵至10⁶M范围内。圆二色光谱研究证实了加入分子后DNA诱导的构象变化。在DNA的负峰和正峰均观察到椭圆率的变化，因此表明分子发生了嵌入。加入DNA后观察到溴化乙锭从DNA上的位移以及Tm升高，证实了结合的嵌入模式。计算对接进一步验证了这一点，其显示分子清晰地嵌入受体DNA的d(GpC)-d(CpG)位点。使用MTT法评估了这些分子的抗癌活性。两种分子对所研究的所有三种癌细胞均显示出抗增殖活性，其中羟基 - DPTQ在两者中更具潜力。羟基 - DPTQ和甲氧基 - DPTQ的IC₅₀值分别在3 - 5μM和130 - 250μM范围内。
