Effect of coordination mode of thiosemicarbazone on the biological activities of its Ru(II)-benzene complexes: Biomolecular interactions and anticancer activity via ROS-mediated mitochondrial apoptosis

被引:9
作者
Haribabu, Jebiti [1 ]
Arulkumar, Rasu [2 ]
Mahendiran, Dharmasivam [3 ]
Jeyalakshmi, Kumaramangalam [4 ]
Swaminathan, Srividya [5 ]
Venuvanalingam, Ponnambalam [2 ]
Bhuvanesh, Nattamai [6 ]
Santibanez, Juan F. [7 ,8 ]
Karvembu, Ramasamy [9 ]
机构
[1] Univ Atacama, Fac Med, Carreras 1579, Copiapo 1532502, Chile
[2] Bharathidasan Univ, Sch Chem, Theoret & Computat Chem Lab, Tiruchirappalli 620024, India
[3] Univ Sydney, Dept Pathol, Bosch Inst, Sydney, NSW 2006, Australia
[4] M Kumarasamy Coll Engn, Dept Chem, Karur 639113, India
[5] Chennai Inst Technol CIT, Ctr Computat Modeling, Chennai 600069, India
[6] Texas A&M Univ, Dept Chem, College Stn, TX 77842 USA
[7] Univ Belgrade, Inst Med Res, Natl Inst Republ Serbia, Belgrade, Serbia
[8] Bernardo OHiggins Univ, Integrat Ctr Biol & Appl Chem CIBQA, Santiago, Chile
[9] Natl Inst Technol, Dept Chem, Tiruchirappalli 620015, India
关键词
Thiosemicarbazones; Ru(II)-benzene complexes; Biomolecular interactions; Anticancer activity; Apoptosis; RUTHENIUM(II) ARENE COMPLEXES; ANTIPARASITIC ACTIVITY; CYTOTOXIC ACTIVITY; SERUM-ALBUMIN; BINDING; BENZALDEHYDE; CRYSTAL; DERIVATIVES; KP1019; SERIES;
D O I
10.1016/j.ica.2024.121973
中图分类号
O61 [无机化学];
学科分类号
070301 ; 081704 ;
摘要
Ru(II)-benzene complexes (P1 and P2) were synthesized using a thiosemicarbazone ligand (L1) in two different coordination modes, monodentate S and bidentate N,S, through carefully adjusted reaction conditions. Comprehensive characterization of the complexes was achieved through single crystal X-ray diffraction, revealing a piano-stool geometry around the Ru(II) ion. To evaluate the binding capabilities of the complexes towards CT DNA and BSA, UV-Vis and/or hydrodynamic methods were utilized. Docking studies further validated the intercalative binding mode with DNA, in agreement with the experimental findings, and identified specific BSA amino acids involved in the binding interactions. Based on the results of binding studies, cytotoxicity of the ligand and complexes was appraised in various cancer and normal cell lines alongside the commercial pharmaceutics. Complexes P1 and P2 displayed a promising activity against MDA-MB-231 [IC50 = 5.11 (P1) and 3.48 mu M (P2)] and PANC-1 [IC50 = 7.20 (P1) and 4.85 mu M (P2)] cancer cells; with the bidentate system (P2) exhibiting a higher activity than its monodentate congener P1, although both of them showed superior activity than the reference drugs. Various bioassays including Western blot analysis revealed the mode of cell death to be apoptosis, which was further concluded to be via the ROS-mediated mitochondrial signaling pathway.
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页数:11
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共 53 条
  • [1] Improved antiparasitic activity by incorporation of organosilane entities into half-sandwich ruthenium(II) and rhodium(III) thiosemicarbazone complexes
    Adams, Muneebah
    de Kock, Carmen
    Smith, Peter J.
    Land, Kirkwood M.
    Liu, Nicole
    Hopper, Melissa
    Hsiao, Allyson
    Burgoyne, Andrew R.
    Stringer, Tameryn
    Meyer, Mervin
    Wiesner, Lubbe
    Chibale, Kelly
    Smith, Gregory S.
    [J]. DALTON TRANSACTIONS, 2015, 44 (05) : 2456 - 2468
  • [2] The synthesis and antiparasitic activity of aryl- and ferrocenyl-derived thiosemicarbazone ruthenium(II)-arene complexes
    Adams, Muneebah
    Li, Yiqun
    Khot, Heena
    De Kock, Carmen
    Smith, Peter J.
    Land, Kirkwood
    Chibale, Kelly
    Smith, Gregory S.
    [J]. DALTON TRANSACTIONS, 2013, 42 (13) : 4677 - 4685
  • [3] Ruthenium antimetastatic agents
    Alessio, E
    Mestroni, G
    Bergamo, A
    Sava, G
    [J]. CURRENT TOPICS IN MEDICINAL CHEMISTRY, 2004, 4 (15) : 1525 - 1535
  • [4] Influence of Indole-N Substitution of Thiosemicarbazones in Cationic Ru(II)(η6-Benzene) Complexes on Their Anticancer Activity
    Balakrishnan, Nithya
    Haribabu, Jebiti
    Dharmasivam, Mahendiran
    Jayadharini, Jayachandra Prakasan
    Anandakrishnan, Dhanabalan
    Swaminathan, Srividya
    Bhuvanesh, Nattamai
    Echeverria, Cesar
    Karvembu, Ramasamy
    [J]. ORGANOMETALLICS, 2023, 42 (03) : 259 - 275
  • [5] Half-sandwich ruthenium-arene complexes with thiosemicarbazones: Synthesis and biological evaluation of [(η6-p-cymene)Ru(piperonal thiosemicarbazones)Cl]Cl complexes
    Beckford, Floyd
    Dourth, Deidra
    Shaloski, Michael, Jr.
    Didion, Jacob
    Thessing, Jeffrey
    Woods, Jason
    Crowell, Vernon
    Gerasimchuk, Nikolay
    Gonzalez-Sarrias, Antonio
    Seeram, Navindra P.
    [J]. JOURNAL OF INORGANIC BIOCHEMISTRY, 2011, 105 (08) : 1019 - 1029
  • [6] Synthesis and structure of [(η6-p-cymene)Ru(2-anthracen-9-ylmethylene-N- ethylhydrazinecarbothioamide)Cl]Cl; biological evaluation, topoisomerase II inhibition and reaction with DNA and human serum albumin
    Beckford, Floyd
    Thessing, Jeffrey
    Woods, Jason
    Didion, Jacob
    Gerasimchuk, Nikolay
    Gonzalez-Sarrias, Antonio
    Seeram, Navindra P.
    [J]. METALLOMICS, 2011, 3 (05) : 491 - 502
  • [7] Organometallic ruthenium complexes with thiosemicarbazone ligands: Synthesis, structure and cytotoxicity of [(η6-p-cymene)Ru(NS)Cl]+ (NS=9-anthraldehyde thiosemicarbazones)
    Beckford, Floyd A.
    Leblanc, Gabriel
    Thessing, Jeffrey
    Shaloski, Michael, Jr.
    Frost, Brian J.
    Li, Liya
    Seeram, Navindra P.
    [J]. INORGANIC CHEMISTRY COMMUNICATIONS, 2009, 12 (11) : 1094 - 1098
  • [8] ARENE RUTHENIUM(II) COMPLEXES FORMED BY DEHYDROGENATION OF CYCLOHEXADIENES WITH RUTHENIUM(III) TRICHLORIDE
    BENNETT, MA
    SMITH, AK
    [J]. JOURNAL OF THE CHEMICAL SOCIETY-DALTON TRANSACTIONS, 1974, (02): : 233 - 241
  • [9] Biological role of adduct formation of the ruthenium(III) complex NAMI-A with serum albumin and serum transferrin
    Bergamo, A
    Messori, L
    Piccioli, F
    Cocchietto, M
    Sava, G
    [J]. INVESTIGATIONAL NEW DRUGS, 2003, 21 (04) : 401 - 411
  • [10] Enhancing the Activity of Drugs by Conjugation to Organometallic Fragments
    Chellan, Prinessa
    Sadler, Peter J.
    [J]. CHEMISTRY-A EUROPEAN JOURNAL, 2020, 26 (40) : 8676 - 8688