A comparative study of novel ruthenium(III) and iron(III) complexes containing uracil; docking and biological studies.

Autor: Althobaiti F; Department of Biotechnology, College of Science, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia. Electronic address: faiz@tu.edu.sa., Sahyon HA; Chemistry Department, Faculty of Science, Kafrelsheikh University, 33516 Kafrelsheikh, Egypt. Electronic address: heba_sahuon@sci.kfs.edu.eg., Shanab MMAH; Department of Chemistry, College of Sciences and Humanities Studies (Girls section), Hawtat Bani Tamim 11149, Prince Sattam Bin Abdulaziz University, P.O. Box:13, Saudi Arabia. Electronic address: m.hassan@psau.edu.sa., Aldhahrani A; Clinical Laboratory Science Department, Turabah University College, Taif University, Taif 21995, Saudi Arabia. Electronic address: a.ahdhahrani@tu.edu.sa., Helal MA; Chemistry Department, Faculty of Science, Damietta University, Damietta, Egypt., Khireldin A; Air transport management, Singapore Institute of Technology (SIT), Singapore. Electronic address: Awad.Khireldin@singaporetech.edu.sg., Shoair AGF; Department of Science and Technology, University College-Ranyah, postcode 21975, Taif University, Saudi Arabia; High Altitude Research Center, Taif University, 21944, Saudi Arabia. Electronic address: afshaair@tu.edu.sa., Almalki ASA; Chemistry Department, Faculty of Science, Taif University, Taif 21974, Saudi Arabia., Fathy AM; Chemistry Department, Faculty of Science, Zagazig University, Zagazig, Egypt.
Jazyk: angličtina
Zdroj: Journal of inorganic biochemistry [J Inorg Biochem] 2023 Oct; Vol. 247, pp. 112308. Date of Electronic Publication: 2023 Jul 05.
DOI: 10.1016/j.jinorgbio.2023.112308
Abstrakt: Structural and biological studies were conducted on the novel complexes [Fe(U) 2 (H 2 O) 2 ]Cl 3 (FeU) and [Ru(U) 2 (H 2 O) 2 ]Cl 3 (RuU) (U = 5,6-Diamino-1,3-dimethylpyrimidine-2,4(1H,3H)-dione) to develop an anticancer drug candidate. The two complexes have been synthesized and characterized. Based on our findings, these complexes have octahedral geometry. The DNA-binding study proved that both complexes coordinated with CT-DNA. The docking study confirmed the potency of both complexes in downregulating the topoisomerase I protein through their high binding affinity. Biological studies have established that both complexes can act as potent anticancer agents against three cancer cell lines. RuU or FeU complexes induce apoptosis in breast cancer cells by increasing caspase9 protein and inhibiting proliferating cell nuclear antigen (PCNA) activity. In addition, both complexes down-regulate topoisomerase I expression in breast cancer cells. Therefore, the RuU and FeU complexes' anticancer activities were mediated via both apoptosis induction and topoisomerase I down-regulation. In conclusion, both complexes have dual anticancer activity pathways that may be responsible for the selective cytotoxicity of the complexes. This makes them more suitable for the development of novel cancer treatment strategies.
Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest to be reported.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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