Ruthenium(II) Complexes as Potential Apoptosis Inducers in Cancer Therapy

Zaric, Radica Zivkovic; Pirkovic, Marijana Stanojevic; Hamzagic, Nedim

doi:10.2478/sjecr-2019-0016

Abstract

The compound cis-diamminedichloroplatinum(II) (cisplatin) is the most widely used anticancer drug, but due to its serious side effects (including gastrointestinal symptoms, renal tubular injury, neuromuscular complications, and ototoxicity), clinical applications of cisplatin are limited. Therefore, these limitations have provided an encouragement for further research into other transition metal complexes, with an aim to overcome the disadvantages related with cisplatin therapy. In the search for effective complexes that can be targeted against tumor cells, many research groups synthesized various ruthenium(II) complexes with different ligands. Also, newly synthesized ruthenium(II) complexes showed selective anticancer activity against different types of cancer cells. Activity of ruthenium(II) complexes in some cases was even higher than that of cisplatin against the same cells. Precise mechanism of action of ruthenium(II) complexes is not fully understood. The different examples mentioned in this review showed that ruthenium(II) complexes decreased viability of cancer cells by induction of apoptosis and/or by cell cycle arrest which implies their different mechanism of action against different types of cancer cells.

References

Lazić D, Arsenijević A, Puchta R, Bugarčić ŽD, Rilak A. DNA binding properties, histidine interaction and cytotoxicity studies of water soluble ruthenium(ii) terpyridine complexes. Dalton Trans. 2016;45(11):4633-46.
Search in Google Scholar Back to article
Motswainyana M, Ajibade P. Anticancer activities of mononuclear ruthenium (II) coordination complexes. Advances in Chemistry. 2015;2015:859730.
Search in Google Scholar Back to article
Kljun J, Petricek S, Zigon D, Hudej R, Miklavcic D, Turel I. Synthesis and Characterization of Novel Ruthenium(III) Complexes with Histamine. Bioinorg Chem Appl. 2010;2010:183097.
Search in Google Scholar Back to article
Antonarakis ES, Emadi A. Ruthenium-based chemotherapeutics: are they ready for prime time? Cancer Chemother Pharmacol. 2010;66(1):1-9.
Search in Google Scholar Back to article
Pongratz M, Schluga P, Jakupec MA, Arion VB, Hartinger CG, et al. Transferrin binding and transferrinmediated cellular uptake of the ruthenium coordination compound KP1019, studied by means of AAS, ESI-MS and CD spectroscopy. J Anal At Spectrom. 2004; 19:46–51.
Search in Google Scholar Back to article
Mari C, Pierroz V, Ferrari S, Gasser G. Combination of Ru(II) complexes and light: new frontiers in cancer therapy. Chem Sci. 2015;6(5):2660-86.
Search in Google Scholar Back to article
Zeng L, Gupta P, Chen Y, et al. The development of anti-cancer ruthenium(ii) complexes: from single molecule compounds to nanomaterials. Chem Soc Rev. 2017;46(19):5771-804.
Search in Google Scholar Back to article
Gkionis K, Platts JA, Hill JG. Insights into DNA binding of ruthenium arene complexes: role of hydrogen bonding and pistacking. Inorg Chem. 2008;47(9):3893-902.
Search in Google Scholar Back to article
Čanović P, Simović AR, Radisavljević S, Bratsos I, Demitri N, Mitrović M, Zelen I, Bugarčić ŽD. Impact of aromaticity on anticancer activity of polypyridylruthenium(II) complexes: synthesis, structure, DNA/protein binding, lipophilicity and anticancer activity. J BiolInorg Chem. 2017;22(7):1007-28.
Search in Google Scholar Back to article
Urathamakul T, Beck JL, Sheil MM, Aldrich-Wright JR, Ralph SF. A mass spectrometric investigation of non-covalent interactions between ruthenium complexes and DNA. Dalton Trans. 2004;(17):2683-90.
Search in Google Scholar Back to article
Alessio E, Mestroni G, Bergamo A, Sava G. Ruthenium antimetastatic agents. Curr Top Med Chem. 2004;4(15):1525-35.
Search in Google Scholar Back to article
Coverdale JP, Laroiya-McCarron T, Romero-Canelón I. Designing Ruthenium Anticancer Drugs: What Have We Learnt from the Key Drug Candidates?. Inorganics. 2019;7(3):31.
Search in Google Scholar Back to article
Zhang L, Carroll P, Meggers E. Ruthenium complexes as protein kinase inhibitors. Org Lett. 2004;6(4):521-3.
Search in Google Scholar Back to article
Williams DS, Carroll PJ, Meggers E. Platinum complex as a nanomolar protein kinase inhibitor. Inorg Chem. 2007;46(8):2944-6.
Search in Google Scholar Back to article
Maksimoska J, Feng L, Harms K, Yi C, Kissil J, Marmorstein R, Meggers E. Targeting large kinase active site with rigid, bulky octahedral ruthenium complexes. J Am Chem Soc. 2008;130(47):15764-5.
Search in Google Scholar Back to article
Bregman H, Meggers E. Ruthenium half-sandwich complexes as protein kinase inhibitors: an N-succinimidyl ester for rapid derivatizations of the cyclopentadienyl moiety. Org lett. 2006;8(24):5465-8.
Search in Google Scholar Back to article
Pagano N, Maksimoska J, Bregman H, Williams DS, Webster RD, Xue F, Meggers E. Ruthenium half-sandwich complexes as protein kinase inhibitors: derivatization of the pyridocarbazole pharmacophore ligand. Org Biomol Chem. 2007;5(8):1218-27.
Search in Google Scholar Back to article
Meggers E, Atilla-Gokcumen GE, Bregman H, Maksimoska J, Mulcahy SP, Pagano N, Williams DS. Exploring chemical space with organometallics: ruthenium complexes as protein kinase inhibitors. Synlett. 2007;2007(8):1177-89.
Search in Google Scholar Back to article
Bregman H, Carroll PJ, Meggers E. Rapid access to unexplored chemical space by ligand scanning around a ruthenium center: discovery of potent and selective protein kinase inhibitors. J Am Chem Soc. 2006;128(3):877-84.
Search in Google Scholar Back to article
Debreczeni JÉ, Bullock AN, Atilla GE, Williams DS, Bregman H, Knapp S, Meggers E. Ruthenium Half‐Sandwich Complexes Bound to Protein Kinase Pim‐1. Angew Chem Int Ed Engl. 2006;45(10):1580-5.
Search in Google Scholar Back to article
Evan GI, Vousden KH. Proliferation, cell cycle and apoptosis in cancer. Nature. 2001;411(6835):342-8.
Search in Google Scholar Back to article
Pietenpol JA, Stewart ZA. Cell cycle checkpoint signaling: Cell cycle arrest versus apoptosis. Toxicology. 2002;181:475-81.
Search in Google Scholar Back to article
Luo Z, Yu L, Yang F, Zhao Z, Yu B, Lai H, Wong KH, Ngai SM, Zheng W, Chen T. Ruthenium polypyridyl complexes as inducer of ROS-mediated apoptosis in cancer cells by targeting thioredoxin reductase. Metallomics. 2014;6(8):1480-90.
Search in Google Scholar Back to article
Thota S, Rodrigues DA, Crans DC, Barreiro EJ. Ru (II) compounds: next-generation anticancer metallotherapeutics?. J Med Chem. 2018;61(14):5805-21.
Search in Google Scholar Back to article
Zheng K, Wu Q, Wang C, Tan W, Mei W. Ruthenium(II) Complexes as Potential Apoptosis Inducers in Chemotherapy. Anticancer Agents Med Chem. 2017;17(1):29-39.
Search in Google Scholar Back to article
Costa CO, Neto JH, Baliza IR, Dias RB, Valverde LD, Vidal MT, Sales CB, Rocha CA, Moreira DR, Soares MB, Batista AA. Novel piplartine-containing ruthenium complexes: synthesis, cell growth inhibition, apoptosis induction and ROS production on HCT116 cells. Oncotarget. 2017;8(61):104367-92.
Search in Google Scholar Back to article
Tian M, Li J, Zhang S, Guo L, He X, Kong D, Zhang H, Liu Z. Half-sandwich ruthenium (ii) complexes containing N^ N-chelated imino-pyridyl ligands that are selectively toxic to cancer cells. Chemical Communications. 2017;53(95):12810-3.
Search in Google Scholar Back to article
Coverdale JP, Romero-Canelón I, Sanchez-Cano C, Clarkson GJ, Habtemariam A, Wills M, Sadler PJ. Asymmetric transfer hydrogenation by synthetic catalysts in cancer cells. Nature chemistry. 2018;10(3):347-354.
Search in Google Scholar Back to article
29. Chow MJ, Babak MV, Tan KW, Cheong MC, Pastorin G, Gaiddon C, Ang WH. Induction of the Endoplasmic Reticulum Stress Pathway by Highly Cytotoxic Organoruthenium Schiff-Base Complexes. Molecular Pharmaceutics 2018;15(8):3020–31.
Search in Google Scholar Back to article
Xu L, Zhang PP, Fang XQ, Liu Y, Wang JQ, Zhou HZ, Chen ST, Chao H. A ruthenium(II) complex containing a p-cresol group induces apoptosis in human cervical carcinoma cells through endoplasmic reticulum stress and reactive oxygen species production. Journal of Inorganic Biochemistry 2019;191:126–34.
Search in Google Scholar Back to article
Lin K, Zhao ZZ, Bo HB, Hao XJ, Wang JQ. Applications of Ruthenium Complex in Tumor Diagnosis and Therapy. Front Pharmacol. 2018;9:1323.
Search in Google Scholar Back to article
Gill MR, Cecchin D, Walker MG, Mulla RS, Battaglia G, Smythe C, Thomas JA. Targeting the endoplasmic reticulum with a membrane-interactive luminescent ruthenium(ii) polypyridyl complex. Chem Sci. 2013;4(12):4512-9.
Search in Google Scholar Back to article
Flocke LS, Trondl R, Jakupec MA, Keppler BK. Molecular mode of action of NKP-1339 - a clinically investigated ruthenium-based drug - involves ER- and ROS-related effects in colon carcinoma cell lines. Invest New Drugs. 2016;34(3):261-8.
Search in Google Scholar Back to article
Li Y, Zhu D, Hou L, Hu B, Xu M, Meng X. TRB3 reverses chemotherapy resistance and mediates crosstalk between endoplasmic reticulum stress and AKT signaling pathways in MHCC97H human hepatocellular carcinoma cells. Oncol Lett. 2018;15(1):1343-9.
Search in Google Scholar Back to article
Hassan M, Selimovic D, Hannig M, Haikel Y, Brodell RT, Megahed M. Endoplasmic reticulum stress-mediated pathways to both apoptosis and autophagy: Significance for melanoma treatment. World J Exp Med. 2015;5(4):206-17.
Search in Google Scholar Back to article
Tomás-Gamasa M, Martínez-Calvo M, Couceiro JR, Mascareñas JL. Transition metal catalysis in the mitochondria of living cells. Nat Commun. 2016;7:12538.
Search in Google Scholar Back to article
Qian C, Wang JQ, Song CL, Wang LL, Ji LN, Chao H. The induction of mitochondria-mediated apoptosis in cancer cells by ruthenium(II) asymmetric complexes. Metallomics. 2013;5(7):844-54.
Search in Google Scholar Back to article
Mortezaee K, Salehi E, Mirtavoos-Mahyari H, Motevaseli E, Najafi M, Farhood B, Rosengren RJ, Sahebkar A. Mechanisms of apoptosis modulation by curcumin: Implications for cancer therapy. J Cell Physiol. 2019; doi: 10.1002/jcp.28122.
Search in Google Scholar Back to article
Guzmán EA. Regulated Cell Death Signaling Pathways and Marine Natural Products That Target Them. Mar Drugs. 2019; doi: 10.3390/md17020076.
Search in Google Scholar Back to article
Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol. 2007;35(4):495-516.
Search in Google Scholar Back to article
Guicciardi ME, Gores GJ. Life and death by death receptors. FASEB J. 2009;23(6):1625-37.
Search in Google Scholar Back to article
Xiong S, Mu T, Wang G, Jiang X. Mitochondria-mediated apoptosis in mammals. Protein Cell. 2014;5(10):737-49.
Search in Google Scholar Back to article
Green DR, Llambi F. Cell Death Signaling. Cold Spring Harb Perspect Biol. 2015;7(12). pii: a006080.
Search in Google Scholar Back to article
Tam ZY, Cai YH, Gunawan R. Elucidating cytochrome C release from mitochondria: insights from an in silico three-dimensional model. Biophys J. 2010;99(10):3155-63.
Search in Google Scholar Back to article
Ryter SW, Cloonan SM, Choi AM. Autophagy: a critical regulator of cellular metabolism and homeostasis. Mol Cells. 2013;36(1):7-16.
Search in Google Scholar Back to article
Yang ZJ, Chee CE, Huang S, Sinicrope FA. The role of autophagy in cancer: therapeutic implications. Mol Cancer Ther. 2011;10(9):1533-41.
Search in Google Scholar Back to article
Fink SL, Cookson BT. Apoptosis, pyroptosis, and necrosis: mechanistic description of dead and dying eukaryotic cells. Infect Immun. 2005;73(4):1907-16.
Search in Google Scholar Back to article
Kroemer G, Galluzzi L, Vandenabeele P, et al. Classification of cell death: recommendations of the Nomenclature Committee on Cell Death 2009. Cell Death Differ. 2008;16(1):3-11.
Search in Google Scholar Back to article
Rock KL, Kono H. The inflammatory response to cell death. Annu Rev Pathol. 2008;3:99-126.
Search in Google Scholar Back to article
Valencia A, Morán J. Reactive oxygen species induce different cell death mechanisms in cultured neurons. Free Radic Biol Med. 2004;36(9):1112-25.
Search in Google Scholar Back to article
Havrylyuk D, Deshpande M, Parkin S, Glazer EC. Ru(ii) complexes with diazine ligands: electronic modulation of the coordinating group is key to the design of “dual action” photoactivated agents. Chem Commun (Camb). 2018;54(88):12487-90.
Search in Google Scholar Back to article
Biancalana L, Pampaloni G, Marchetti F. Arene Ruthenium(II) Complexes with Phosphorous Ligands as Possible Anticancer Agents. Chimia (Aarau). 2017;71(9):573-9.
Search in Google Scholar Back to article
Haghdoost MM, Guard J, Golbaghi G, Castonguay A. Anticancer Activity and Catalytic Potential of Ruthenium(II)-Arene Complexes with N,O-Donor Ligands. Inorg Chem. 2018;57(13):7558-67.
Search in Google Scholar Back to article
Gopal YN, Jayaraju D, Kondapi AK. Inhibition of topoisomerase II catalytic activity by two ruthenium compounds: a ligand-dependent mode of action. Biochemistry. 1999;38(14):4382-8.
Search in Google Scholar Back to article
Jeyalakshmi K, Haribabu J, Balachandran C, S. P. Bhuvanesh S. P N, Emib N, Karvembu R. Synthesis of Ru(II)-benzene complexes containing aroylthiourea lig- and, and their binding with biomolecules and in vitro cytotoxicity through apoptosis. New J Chem. 2017;41(7): 2672-86.
Search in Google Scholar Back to article
Milutinović MM, Rilak A, Bratsos I, Klisurić O, Vraneš M, Gligorijević N, Radulović S, Bugarčić ŽD. New 4′-(4- chlorophenyl)-2, 2′: 6′, 2 ″-terpyridine ruthenium (II) complexes: synthesis, characterization, interaction with DNA/BSA and cytotoxicity studies. Journal of inorganic biochemistry. 2017;169:1-2.
Search in Google Scholar Back to article
Liao G, Chen X, Wu J, Qian C, Wang Y, Ji L, Chao H. Ruthenium (ii) polypyridyl complexes as dual inhibitors of telomerase and topoisomerase. Dalton Trans. 2015;44(34):15145-56.
Search in Google Scholar Back to article
Mazuryk O, Suzenet F, Kieda C, Brindell M. The biological effect of the nitroimidazole derivative of a polypyridyl ruthenium complex on cancer and endothelial cells. Metallomics. 2015;(3):553-66.
Search in Google Scholar Back to article
D’Sousa Costa CO, AraujoNeto JH, Baliza IRS, et al. Novel piplartine-containing ruthenium complexes: synthesis, cell growth inhibition, apoptosis induction and ROS production on HCT116 cells. Oncotarget. 2017; 8(61):104367-92.
Search in Google Scholar Back to article
Gill MR, Cecchin D, Walker MG, et al. Targeting the endoplasmic reticulum with a membrane-interactive luminescent ruthenium(ii) polypyridylcomplex†Electronic supplementary information (ESI) available. Chem Sci. 2013;4(12):4512-4519.
Search in Google Scholar Back to article
Tan CP, Lu YY, Ji LN, Mao ZW. Metallomics insights into the programmed cell death induced by metal-based anticancer compounds. Metallomics. 2014;6(5):978-95.
Search in Google Scholar Back to article
Han BJ, Jiang GB, Wang J, Li W, Huang HL, Liu YJ. The studies on bioactivity in vitro of ruthenium (II) polypyridyl complexes towards human lung carcinoma A549 cells. RSC Advances. 2014;4(77):40899-906.
Search in Google Scholar Back to article
Lai SH, Li W, Wang XZ, Zhang C, Zeng CC, Tang B, Wan D, Liu YJ. Apoptosis, autophagy, cell cycle arrest, cell invasion and BSA-binding studies in vitro of ruthenium (II) polypyridyl complexes. RSC Advances. 2016;6(68):63143-55.
Search in Google Scholar Back to article
Poynton FE, Bright SA, Blasco S, Williams DC, Kelly JM, Gunnlaugsson T. The development of ruthenium (II) polypyridyl complexes and conjugates for in vitro cellular and in vivo applications. Chem Soc Rev. 2017;46(24):7706-56.
Search in Google Scholar Back to article
Sahu AK, Dash DK, Mishra K, Mishra SP, Yadav R, Kashyap P. Properties and Applications of Ruthenium. Noble and Precious Metals - Properties, Nanoscale Effects and Applications. InTech; 2018.
Search in Google Scholar Back to article
Adeniyi AA, Ajibade PA. Development of ruthenium- based complexes as anticancer agents: toward a rational design of alternative receptor targets. Reviews in Inorganic Chemistry 2016;36(2).
Search in Google Scholar Back to article
Englinger B, Pirker C, Heffeter P, Terenzi A, Kowol CR, Keppler BK, Berger W. Metal Drugs and the Anticancer Immune Response. Chem Rev. 2018; doi: 10.1021/acs.chemrev.8b00396.
Search in Google Scholar Back to article
Weiss A, Berndsen RH, Dubois M, Müller C, Schibli R, Griffioen AW, Dyson PJ, Nowak-Sliwinska P. In vivo anti-tumor activity of the organometallic ruthenium(ii)- arene complex [Ru(η6-p-cymene)Cl2(pta)] (RAPTA-C) in human ovarian and colorectal carcinomas. Chem Sci. 2014;5(12):4742–8.
Search in Google Scholar Back to article
Sun W, Li S, Häupler B, Liu J, Jin S, Steffen W, Schubert US, Butt HJ, Liang XJ, Wu S. An Amphiphilic Ruthenium Polymetallodrug for Combined Photodynamic Therapy and Photochemotherapy In Vivo. Adv Mater. 2017;29(6):1603702.
Search in Google Scholar Back to article
Chen ZF, Qin QP, Qin JL, Zhou J, Li YL, Li N, Liu YC, Liang H. Water-soluble ruthenium (II) complexes with chiral 4-(2, 3-dihydroxypropyl)-formamide oxoaporphine (FOA): in vitro and in vivo anticancer activity by stabilization of G-Quadruplex DNA, inhibition of telomerase activity, and induction of tumor cell apoptosis. J Med Chem. 2015;58(11):4771-89.
Search in Google Scholar Back to article
Haghdoost M, Golbaghi G, Létourneau M, Patten SA, Castonguay A. Lipophilicity-antiproliferative activity relationship study leads to the preparation of a ruthenium (II) arene complex with considerable in vitro cytotoxicity against cancer cells and a lower in vivo toxicity in zebrafish embryos than clinically approved cis-platin. Eur J Med Chem. 2017;132:282-93.
Search in Google Scholar Back to article
Wang JQ, Zhang PY, Ji LN, Chao H. A ruthenium (II) complex inhibits tumor growth in vivo with fewer side- effects compared with cisplatin. J Inorg Biochem. 2015;146:89-96.
Search in Google Scholar Back to article
Kwong WL, Lam KY, Lok CN, Lai YT, Lee PY, Che CM. A Macrocyclic Ruthenium (III) Complex Inhibits Angiogenesis with Down‐Regulation of Vascular Endothelial Growth Factor Receptor‐2 and Suppresses Tumor Growth In Vivo. Angew Chem Int Ed Engl. 2016;55(43):13524-8.
Search in Google Scholar Back to article
Fong J, Kasimova K, Arenas Y, Kaspler P, Lazic S, Mandel A, Lilge L. A novel class of ruthenium-based photo- sensitizers effectively kills in vitro cancer cells and in vi- vo tumors. Photochem Photobiol Sci. 2015;14(11):2014- 23.
Search in Google Scholar Back to article
Lazarević T, Rilak A, Bugarčić ŽD. Platinum, palladium, gold and ruthenium complexes as anticancer agents: Current clinical uses, cytotoxicity studies and future perspectives. Eur J Med Chem. 2017;142:8-31.
Search in Google Scholar Back to article
Milutinović MM, Čanović PP, Stevanović D, Masnikosa R, Vraneš M, Tot A, Zarić MM, Simović Marković B, Misirkić Marjanović M, Vučićević Lj, Savić M, Jakovljević V, Trajković V, Volarević V, Kanjevac T, Rilak Simović A. Newly Synthesized Heteronuclear Ruthenium(II)/Ferrocene Complexes Suppress the Growth of Mammary Carcinoma in 4T1-Treated BALB/c Mice by Promoting Activation of Antitumor Immunity. Organometallics. 2018;37(22):4250–66.
Search in Google Scholar Back to article
Ramu V, Aute S, Taye N, Guha R, Walker MG, Mogare D, Parulekar A, Thomas JA, Chattopadhyay S, Das A. Photo-induced cytotoxicity and anti-metastatic activity of ruthenium (II)–polypyridyl complexes functionalized with tyrosine or tryptophan. Dalton Trans. 2017;46(20):6634-44.
Search in Google Scholar Back to article
Brabec V, Pracharova J, Stepankova J, Sadler PJ, Kasparkova J. Photo-induced DNA cleavage and cytotoxicity of a ruthenium (II) arene anticancer complex. J Inorg Biochem. 2016;160:149-55.
Search in Google Scholar Back to article
Liu J, Chen Y, Li G, Zhang P, Jin C, Zeng L, Ji L, Chao H. Ruthenium (II) polypyridyl complexes as mitochondria-targeted two-photon photodynamic anticancer agents. Biomaterials. 2015;56:140-53.
Search in Google Scholar Back to article
Lameijer LN, Ernst D, Hopkins SL, Meijer MS, Askes SH, Le Dévédec SE, Bonnet S. A Red‐Light‐Activated Ruthenium‐Caged NAMPT Inhibitor Remains Phototoxic in Hypoxic Cancer Cells. Angew Chem Int Ed Engl. 2017;56(38):11549-53.
Search in Google Scholar Back to article
Zeng L, Kuang S, Li G, Jin C, Ji L, Chao H. A GSH- activatable ruthenium (II)-azo photosensitizer for two- photon photodynamic therapy. Chem Commun. 2017;53(12):1977-80.
Search in Google Scholar Back to article
van Rixel VH, Siewert B, Hopkins SL, Askes SH, Busemann A, Siegler MA, Bonnet S. Green light-induced apoptosis in cancer cells by a tetrapyridyl ruthenium pro- drug offering two trans coordination sites. Chem Sci. 2016;7(8):4922-9.
Search in Google Scholar Back to article
Tang TS, Yip AM, Zhang KY, Liu HW, Wu PL, Li KF, Cheah KW, Lo KK. Bioorthogonal labeling, bioimaging, and photocytotoxicity studies of phosphorescent Ruthenium (II) polypyridine dibenzocyclooctyne complexes. Chemistry. 2015;21(30):10729-40.
Search in Google Scholar Back to article
Basu U, Karges J, Chotard F, Balan C, Le Gendre P, Gasser G, Bodio E, Kabbara RM. Investigation of photoactivation on Ruthenium (II)-arene complexes for the discovery of potential selective cytotoxic agents. Polyhedron. 2019; doi: 10.1016/j.poly.2019.02.041.
Search in Google Scholar Back to article
Wei J, Renfrew AK. Photolabile ruthenium complexes to cage and release a highly cytotoxic anticancer agent. J Inorg Biochem. 2018;179:146-53.
Search in Google Scholar Back to article
Ndagi U, Mhlongo N, Soliman ME. Metal complexes in cancer therapy–an update from drug design perspective. Drug Des Devel Ther. 2017;11:599-616.
Search in Google Scholar Back to article
Monro S, Colón KL, Yin H, Roque III J, Konda P, Gujar S, Thummel RP, Lilge L, Cameron CG, McFarland SA. Transition metal complexes and photodynamic therapy from a tumor-centered approach: Challenges, opportunities, and highlights from the development of TLD1433. Chem Rev. 2018;119(2):797-828.
Search in Google Scholar Back to article

Ruthenium(II) Complexes as Potential Apoptosis Inducers in Cancer Therapy

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