Utilizing coordination chemistry through formation of a Cu II -quinalizarin complex to manipulate cell biology: An in vitro, in silico approach.

Autor: Chatterjee S; Department of Chemistry (Inorganic Section), Jadavpur University, Kolkata 700 032, India; Department of Chemistry, Vijaygarh Jyotish Ray College, Kolkata 700 032, India., Jain CK; Cancer Biology & Inflammatory Disorder Division, Indian Institute of Chemical Biology, Kolkata 700 032, India; Infectious Diseases and Immunology Division, Indian Institute of Chemical Biology, Kolkata 700 032, India., Saha T; Department of Chemistry (Inorganic Section), Jadavpur University, Kolkata 700 032, India., Roychoudhury S; Cancer Biology & Inflammatory Disorder Division, Indian Institute of Chemical Biology, Kolkata 700 032, India., Majumder HK; Infectious Diseases and Immunology Division, Indian Institute of Chemical Biology, Kolkata 700 032, India., Das S; Department of Chemistry (Inorganic Section), Jadavpur University, Kolkata 700 032, India. Electronic address: saurabh.das@jadavpuruniversity.in.
Jazyk: angličtina
Zdroj: Journal of inorganic biochemistry [J Inorg Biochem] 2023 Dec; Vol. 249, pp. 112369. Date of Electronic Publication: 2023 Sep 21.
DOI: 10.1016/j.jinorgbio.2023.112369
Abstrakt: Quinalizarin, an analogue of anthracycline anticancer agents, is an anticancer agent itself. A Cu II complex was prepared and characterized by elemental analysis, UV-Vis & IR spectroscopy, mass spectrometry, EPR and DFT. The intention behind the preparation of the complex was to increase cellular uptake, compare its binding with DNA against that of quinalizarin, modulation of semiquinone formation, realization of human DNA topoisomerase I & human DNA topoisomerase II inhibition and observation of anticancer activity. While the first two attributes of complex formation lead to increased efficacy, decrease in semiquinone generation could results in a compromise with efficacy. Inhibition of human DNA topoisomerase makes up this envisaged compromise in free radical activity since the complex shows remarkable ability to disrupt activities of human DNA topoisomerase I and II. The complex unlike quinalizarin, does not catalyze flow of electrons from NADH to O 2 to the extent known for quinalizarin. Hence, decrease in semiquinone or superoxide radical anion could make modified quinalizarin [as Cu II complex] less efficient in free radical pathway. However, it would be less cardiotoxic and that would be advantageous to qualify it as a better anticancer agent. Although binding to calf thymus DNA was comparable to quinalizarin, it was weaker than anthracyclines. Low cost of quinalizarin could justify consideration as a substitute for anthracyclines but the study revealed IC 50 of quinalizarin/Cu II -quinalizarin was much higher than anthracyclines or their complexes. Even then, there is a possibility that Cu II -quinalizarin could be an improved and less costly form of quinalizarin as anticancer agent.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023. Published by Elsevier Inc.)
Databáze: MEDLINE