Synthesis, DNA binding and cytotoxic activity of pyrimido[4′,5′:4,5]thieno(2,3-b)quinoline with 9-hydroxy-4-(3-diethylaminopropylamino) and 8-methoxy-4-(3-diethylaminopropylamino) substitutions

Publication date: January 2018
Source:Journal of Photochemistry and Photobiology B: Biology, Volume 178
Author(s): Hulihalli N. KiranKumar, Heggodu G. RohitKumar, Gopal M. Advirao
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 (Tm) 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 10⁴ to 10⁶M⁻¹. 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 Tm, 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. IC50 value of Hydroxy-DPTQ and Methoxy-DPTQ were in the range of 3–5μM and 130–250μM, respectively.