Organoruthenium metallocycle induced mutation in gld-1 tumor suppression gene in JK1466 strain and appreciable lifespan expansion.

Autor: Nandhini S; Department of Chemistry, Bharathiar University, Coimbatore 641 046, India., Ranjani M; Department of Chemistry, Bharathiar University, Coimbatore 641 046, India., Thiruppathi G; Department of Zoology, Bharathiar University, Coimbatore 641 046, India., Jaithanya YM; Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600025, India., Kalaiarasi G; Department of Chemistry, Bharathiar University, Coimbatore 641 046, India., Ravi M; Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600025, India. Electronic address: ravimano2004@gmail.com., Prabusankar G; Department of Chemistry, Indian Institute of Technology, Hyderabad 502285, India., Malecki JG; Department of Crystallography, Silesia University, Szkolna 9, 40-006 Katowice, Poland., Sundararaj P; Department of Zoology, Bharathiar University, Coimbatore 641 046, India., Prabhakaran R; Department of Chemistry, Bharathiar University, Coimbatore 641 046, India. Electronic address: rpnchemist@buc.edu.in.
Jazyk: angličtina
Zdroj: Journal of inorganic biochemistry [J Inorg Biochem] 2024 Aug; Vol. 257, pp. 112593. Date of Electronic Publication: 2024 May 08.
DOI: 10.1016/j.jinorgbio.2024.112593
Abstrakt: Four Ru(II) complexes (A2-A5) were synthesized from the reaction of coumarin Schiff base ligands (7da2-tsc, 7da3-mtsc, 7da4-etsc and 7da5-ptsc) with [RuHCl(CO)(PPh 3 ) 3 ]. The compounds were characterized by FT-IR, UV-Vis, 1 H, 13 C and 31 P NMR, mass spectrometry and crystallographic analysis. Calf Thymus DNA (CT-DNA) binding studies revealed the intercalative mode of binding of the complexes with DNA. The results of Bovine serum albumin (BSA) binding studies established the interaction between BSA followed static quenching mechanism. The cytotoxic effects of the complexes and the ligands were evaluated against breast (MCF-7 and MDA-MB-231) and lung carcinoma cell lines (A549 and NCI-H460) using MTT assay. Complex A4 demonstrated potent cytotoxic effects on both breast and lung cancer cells. Furthermore, morphological observations and FACS analysis showed the decrease in cell density by complex A4 by induced morphological changes and apoptotic body formation and cell death in both breast and lung cancer cells. Moreover, the invertebrate model Caenorhabditis elegans was employed to assess the in vivo anticancer activity of compound A4. The findings indicated that the treatment with A4 reduced tumor development and significantly extended organismal lifespan by 64 % in the tumoral strain JK1466 without adversely affecting essential physiological functions of the worm. Additionally, A4 demonstrated an upregulation of two crucial antioxidant defense genes. Overall, these results suggested that the compound A4 can be a potential candidate with novel chemotherapeutic applications.
Competing Interests: Declaration of competing interest We authors declare that we are having any conflicts of interest in publishing this current manuscript in Journal of Inorganic Biochemistry as full research article.
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Databáze: MEDLINE
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