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
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2024
Authors
Haribabu, JebitiArulkumar, Rasu
Mahendiran, Dharmasivam
Jeyalakshmi, Kumaramangalam
Swaminathan, Srividya
Venuvanalingam, Ponnambalam
Bhuvanesh, Nattamai
Santibanez, Juan F.
Karvembu, Ramasamy
Article (Published version)
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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 μM (P2)] and PANC-1 [IC50 = 7.20... (P1) and 4.85 μM (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.
Keywords:
Anticancer activity / Apoptosis / Biomolecular interactions / Ru(II)-benzene complexes / ThiosemicarbazonesSource:
Inorganica Chimica Acta, 2024, 565, 121973-Publisher:
- Elsevier
Funding / projects:
- Center for computational modeling, Chennai Institute of Technology (CIT), (CIT/CCM/2023/RP-021)
- BSR Research Fellowship in Science (25-1/2014-15 (BSR)/7-22/2007 (BSR))
- CSIR Emeritus Scientistship (21(0936)/12/EMR-II)
- DST-PURSE HPC facility (SR/FT/LS-113/2009) at Bharathidasan University
- DST-SERB financial assistance (CRG/2022/003145)
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Institut za medicinska istraživanjaTY - JOUR AU - Haribabu, Jebiti AU - Arulkumar, Rasu AU - Mahendiran, Dharmasivam AU - Jeyalakshmi, Kumaramangalam AU - Swaminathan, Srividya AU - Venuvanalingam, Ponnambalam AU - Bhuvanesh, Nattamai AU - Santibanez, Juan F. AU - Karvembu, Ramasamy PY - 2024 UR - http://rimi.imi.bg.ac.rs/handle/123456789/1475 AB - 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 μM (P2)] and PANC-1 [IC50 = 7.20 (P1) and 4.85 μM (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. PB - Elsevier T2 - Inorganica Chimica Acta T1 - 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 SP - 121973 VL - 565 DO - 10.1016/j.ica.2024.121973 ER -
@article{ author = "Haribabu, Jebiti and Arulkumar, Rasu and Mahendiran, Dharmasivam and Jeyalakshmi, Kumaramangalam and Swaminathan, Srividya and Venuvanalingam, Ponnambalam and Bhuvanesh, Nattamai and Santibanez, Juan F. and Karvembu, Ramasamy", year = "2024", abstract = "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 μM (P2)] and PANC-1 [IC50 = 7.20 (P1) and 4.85 μM (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.", publisher = "Elsevier", journal = "Inorganica Chimica Acta", title = "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", pages = "121973", volume = "565", doi = "10.1016/j.ica.2024.121973" }
Haribabu, J., Arulkumar, R., Mahendiran, D., Jeyalakshmi, K., Swaminathan, S., Venuvanalingam, P., Bhuvanesh, N., Santibanez, J. F.,& Karvembu, R.. (2024). 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. in Inorganica Chimica Acta Elsevier., 565, 121973. https://doi.org/10.1016/j.ica.2024.121973
Haribabu J, Arulkumar R, Mahendiran D, Jeyalakshmi K, Swaminathan S, Venuvanalingam P, Bhuvanesh N, Santibanez JF, Karvembu R. 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. in Inorganica Chimica Acta. 2024;565:121973. doi:10.1016/j.ica.2024.121973 .
Haribabu, Jebiti, Arulkumar, Rasu, Mahendiran, Dharmasivam, Jeyalakshmi, Kumaramangalam, Swaminathan, Srividya, Venuvanalingam, Ponnambalam, Bhuvanesh, Nattamai, Santibanez, Juan F., Karvembu, Ramasamy, "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" in Inorganica Chimica Acta, 565 (2024):121973, https://doi.org/10.1016/j.ica.2024.121973 . .