Title
Characterization of a MnII complex of Alizarin suggests attributes explaining a superior anticancer activity: A comparison with anthracycline drugs
Author
Mouli Saha, Soumen Singh, Mousumi Chakraborty, Swagata Mazumdar, Sanjay Kumar, Parimal Karmakar, Saurabh Das
Year
2019
Journal
Polyhedron
Abstract
Alizarin (DHA), a simple analogue of the anthracycline core was used to form a complex with MnII to see if the complex matches the efficacy of anthracyclines. It was characterized by spectroscopic techniques, mass spectrometry and TGA. In the absence of a single crystal, the structure was obtained by computational techniques. Interaction of the complex with DNA at different ionic strength and pH was compared with anthracyclines to see if it addresses some of the shortcomings of hydroxy-9,10-anthraqunones in general and DHA in particular when compared to anthracyclines. Increased affinity of the complex towards DNA and that its binding constant values do not decrease with increase in pH or decrease in ionic strength of the medium are positive attributes of complex formation. This is significant since cancer patients often experience fluctuation of pH and ionic strength in body fluids during treatment that affect efficacy of drugs. The complex decreases the flow of electrons from NADH to molecular oxygen owing to decreased semiquinone formation; a fact important for controlling cardiotoxicity. Experiments on ROS depletion in HeLa, Hep G2 and WI 38 lung fibroblast cells by the H2DCFDA assay suggests a shift in mechanism for the complex from that of DHA. Loss in efficacy due to decrease in semiquinone formation by the complex is made up by other attributes of complex formation that eventually promote cytotoxicity. Compounds were tried on HeLa, Hep G2 and WI 38 lung fibroblast cells. An effort was made to correlate aspects of semiquinone formation, ROS generation and interaction with DNA with results obtained on two cancer cell lines and a normal cell line.
Instrument
J-815, V-630
Keywords
Absorption, Chemical stability, Quantitation, Ligand binding, DNA structure, Circular dichroism, Inorganic chemistry, Biochemistry, Medicinal