Title
Human Topoisomerase I mediated cytotoxicity profile of L-valine-quercetin diorganotin(IV) antitumor drug entities
Author
Sabiha Parveen, Sartaj Tabassum, Farukh Arjmand
Year
2016
Journal
Journal of Organometallic Chemistry
Abstract
New chiral L-/d-valine-quercetin diorganotin(IV) complexes [(CH3)2Sn(Q)(val)] 1L/D, [(C6H5)2Sn(Q)(val)] 2L/D, were synthesized and thoroughly characterized by elemental analysis, mass spectrometry, IR, 1H NMR, 119Sn NMR spectroscopy. Preliminary comparative DNA binding studies on enantiomeric complexes 1L/D and 2L/D were carried out by UV–vis, fluorescence titrations, thermal denaturation and circular dichroic techniques to ascertain their DNA binding propensity. Thermal denaturation studies of complexes in the absence and presence of CT–DNA have been carried out and ΔTm was calculated to be 2–3 °C depicting electrostatic mode of binding corroborated well with the results of UV–vis and fluorescence studies. The intrinsic binding constant, Kb and binding constant, K values revealed that both L-enantiomers of complexes 1 and 2exhibited exceptionally high binding propensity as compared to their D-enantiomers and between L-enantiomers 2L exhibited greatest binding affinity and followed the trend:2L > 1L > 2D > 1D. The cytotoxicity profile of 1L and 2L was studied on four different human cancer cell lines; HeLa, MCF7, Hep-G2, MIA-Pa-Ca-2 by SRB assay which revealed remarkably good cytotoxic activity (with GI50 values of <10 μg mL−1) and 2L exhibited better cytotoxic activity than 1L. Furthermore, the chemotherapeutic action of drug entities was found to be mediated by human Topoisomerase I enzymatic inhibition.
Instrument
J-815
Keywords
Circular dichroism, Secondary structure, Ligand binding, Stereochemistry, Biochemistry