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Detailed account on activation mechanisms of ruthenium coordination complexes and their role as antineoplastic agents.
Eur J Med Chem. 2018 Apr 25; 150:419-445.EJ

Abstract

Ruthenium (Ru) complexes are known for their promising anticancer activity presumably due to octahedral coordination geometry, slow ligand exchange rate, the range of different oxidation states and target specificity. This review article summarizes the physicochemical processes which are responsible for the selectivity of Ru complexes toward cancer cells over the normal cells. Emphasis has been given on the activation mechanism of Ru(III) complex administered as a prodrug and then the release of active species in an acidic environment of cancer cell through normal or photo induced hydrolysis or ligand oxidation. This article also elaborates how active Ru complex can be designed by their rate of hydrolysis, kinetics of ligand exchange, pKa of the aquated species. The article further articulates how Ru complexes inhibit tumor growth via multiple events such as transferrin/albumin binding, ROS generation, inhibition of glutathione-S-transferases and kinases and DNA intercalation. Based on the above understanding, examples of various Ru complexes with their in-vitro cell based cytotoxicity and mechanism of action have been described to make this review comprehensive for future Ru based anticancer drug development. In the end, comments have been made on some emerging concepts regarding lack of innertness of Ru(III) complexes vis-à-vis Ru(II) species.

Authors+Show Affiliations

Jadavpur University, Raja S. C. Mullick Road, Kolkata, West Bengal, 700032, India.CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu, J&K, 180001, India.CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu, J&K, 180001, India. Electronic address: dmukherjee@iiim.ac.in.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

29547831

Citation

Pal, Mousumi, et al. "Detailed Account On Activation Mechanisms of Ruthenium Coordination Complexes and Their Role as Antineoplastic Agents." European Journal of Medicinal Chemistry, vol. 150, 2018, pp. 419-445.
Pal M, Nandi U, Mukherjee D. Detailed account on activation mechanisms of ruthenium coordination complexes and their role as antineoplastic agents. Eur J Med Chem. 2018;150:419-445.
Pal, M., Nandi, U., & Mukherjee, D. (2018). Detailed account on activation mechanisms of ruthenium coordination complexes and their role as antineoplastic agents. European Journal of Medicinal Chemistry, 150, 419-445. https://doi.org/10.1016/j.ejmech.2018.03.015
Pal M, Nandi U, Mukherjee D. Detailed Account On Activation Mechanisms of Ruthenium Coordination Complexes and Their Role as Antineoplastic Agents. Eur J Med Chem. 2018 Apr 25;150:419-445. PubMed PMID: 29547831.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Detailed account on activation mechanisms of ruthenium coordination complexes and their role as antineoplastic agents. AU - Pal,Mousumi, AU - Nandi,Utpal, AU - Mukherjee,Debaraj, Y1 - 2018/03/07/ PY - 2017/08/15/received PY - 2018/03/02/revised PY - 2018/03/03/accepted PY - 2018/3/17/pubmed PY - 2018/4/27/medline PY - 2018/3/17/entrez KW - Anticancer KW - DNA damage KW - Kinase inhibitor KW - Ligand exchange rate KW - Ruthenium-coordination complex KW - Ruthenium-glutathione-S-transferase inhibitors SP - 419 EP - 445 JF - European journal of medicinal chemistry JO - Eur J Med Chem VL - 150 N2 - Ruthenium (Ru) complexes are known for their promising anticancer activity presumably due to octahedral coordination geometry, slow ligand exchange rate, the range of different oxidation states and target specificity. This review article summarizes the physicochemical processes which are responsible for the selectivity of Ru complexes toward cancer cells over the normal cells. Emphasis has been given on the activation mechanism of Ru(III) complex administered as a prodrug and then the release of active species in an acidic environment of cancer cell through normal or photo induced hydrolysis or ligand oxidation. This article also elaborates how active Ru complex can be designed by their rate of hydrolysis, kinetics of ligand exchange, pKa of the aquated species. The article further articulates how Ru complexes inhibit tumor growth via multiple events such as transferrin/albumin binding, ROS generation, inhibition of glutathione-S-transferases and kinases and DNA intercalation. Based on the above understanding, examples of various Ru complexes with their in-vitro cell based cytotoxicity and mechanism of action have been described to make this review comprehensive for future Ru based anticancer drug development. In the end, comments have been made on some emerging concepts regarding lack of innertness of Ru(III) complexes vis-à-vis Ru(II) species. SN - 1768-3254 UR - https://www.unboundmedicine.com/medline/citation/29547831/Detailed_account_on_activation_mechanisms_of_ruthenium_coordination_complexes_and_their_role_as_antineoplastic_agents_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0223-5234(18)30250-2 DB - PRIME DP - Unbound Medicine ER -