Chemical Sciences

Biographical Details:

1998-2002 B.Sc. Chemistry (NUIM)
2002-2007 Ph.D. Bioinorganic Medicinal Chemistry (ITTD/DIT)
2006-2011 Assistant Lecturer of Medicinal Chemistry (DIT)
2008-2011 Arnold F. Graves Research Fellow (Focas Institute)
2011-        Lecturer of Inorganic Chemistry (DCU)

Cover Articles:

July 2012: Toxicology Research In vitro and in vivo studies into the biological activities of 1,10-phenanthroline, 1,10-phenanthroline-5,6-dione and its copper(II) and silver(I) complexes Cover article of the first edition of the new RSC journal Toxicology Research.

July 2011: Medicinal Chemistry Communications Water-soluble bis(1,10-phenanthroline) octanedioate Cu(II) and Mn(II) complexes with unprecedented nano and picomolar in vitro cytotoxicity: promising leads for chemotherapeutic drug development Editorial highlights: Journal front cover, Med. Chem. Comm., July 2011. 01/04/2011 "Hot Article: A step forward in the fight against cancer". 05/07/2011 "HOT: self-cleaving chemical nucleases with unprecedented in vitro cytotoxicity". 01/08/2011 "Water-soluble self-cleaving chemical nucleases".

Research Interests:

Bioinorganic Chemistry:

• Design of metal complexes as probes for non-covalently binding and cutting double-helical DNA.
• Synthesis and therapeutic evaluation of copper and manganese anticancer agents.
• Reactive oxygen species (ROS) and the design of low-mass, metallo-enzyme mimics for superoxide dismutase (SOD) and catalase (CAT).
• Design of metal-based antimicrobial agents.

Funding Opportunities:

Recent Work:

Immunodetection of γ-H2AX foci (green) within nuclei (red) of ovarian SK-OV-3 cancer cells after 96 h drug treatment with our copper(II) agent.

Targeting Cancerous DNA with Chemotherapeutic Copper Agents Free Radical Biology and Medicine 53 (2012) 564 to 576 Two square-planar copper(II) complexes were designed with structures based on the coordination geometry of the second generation clinical platinum chemotherapeutic drugs. These new compounds displayed DNA binding activity and excellent ability to generate reactive oxygen species (ROS). This combination produced significant in vitro anticancer activity against a range of cell lines (breast, prostate, colon and ovarian). The presence of double-strand DNA breaks was confirmed within ovarian (SK-OV-3) cancer cells using immunodetection of γ-H2AX foci by confocal microscopy and flow cytometry. The SK-OV-3 cell line is known to be intrinsically resistant to the platinum drug, cisplatin, and, interestingly, one of the copper(II) compounds in this study showed strong in vitro potential against that particular cancer cell line.

Designing Potent Oxidative DNA Cleavage Agents Chemical Communications, 2012, 48, 6906 to 6908 In this study we present a detailed analysis of the self-active oxidative DNA cutting profile of a synthetic dinuclear copper(II) complex (pictured left) using plasmid DNA. Direct comparisons were made with the activity of the known artificial metallo-nuclease, copper(II) bis-1,10-phenanthroline chloride. We employed unique experimental design to identify site-specific DNA cleavage of our di-copper compound along with evidence showing that the self-active cleavage mechanism is oxidatively linked. The in vitro cytotoxicity of our agent against the platinum-resistant, human-derived ovarian cancer, SK-OV-3, and non-tumorigenic human-derived ovarian cells, HS-832, was conducted, with activity comparing favourably to the clinical, type II topoisomerase inhibitor, mitoxantrone. Direct evidence of intracellular ROS generation, within human cancer cells, by our di-copper(II) agent is also revealed.

Selected Peer Reviewed Journals

• Dr. Andrew Kellett. .
• McCann M., Santos A., da Silva B., Romanos M., Pyrrho A., Devereux M., Kavanagh K., Fichtner I. and Kellett A. 2012. In vitro and in vivo studies into the biological activities of 1,10-phenanthroline, 1,10-phenanthroline-5,6-dione and its copper(II) and silver(I) complexes. Toxicology Research, 1, 1, pp47-54.
• Prisecaru A., Devereux M., Barron N., McCann M., Colleran J., Casey A., McKee V. and Kellett A. 2012. Potent oxidative DNA cleavage by the di-copper cytotoxin: [Cu2(terephthalate)(1,10-phen)4]2+. Chemical Communications, 48, 55, pp6906-6908.
• Kellett A., Howe O., OConnor M., McCann M., Creaven B., McClean S., Foltyn-Arfa Kia A., Casey A. and Devereux M. 2012. Radical Induced DNA Damage by Cytotoxic Square-Planar Copper(II) Complexes Incorporating o-Phthalate and 1,10-Phenanthroline or 2,2'-Dipyridyl. Free Radical Biology And Medicine, In Press,
• Malachy McCann, Andrew Kellett, Kevin Kavanagh, Michael Devereux and André L. S. Santos. 2012. Deciphering the Antimicrobial Activity of Phenanthroline Chelators. Current Medicinal Chemistry, 19, 17, pp2703-2714.
• McCann M., Curran R., Ben-Shoshan M., McKee V., Tahir A., Devereux M., Kavanagh K., Creaven B. and Kellett A. 2012. Silver(I) complexes of 9-anthracenecarboxylic acid and imidazoles: synthesis, structure and antimicrobial activity. Dalton Transactions, 41, 21, pp6516-6527.
• O'Connor M., Kellett A., McCann M., Rosair G., McNamara M., Howe O., Creaven B., McClean S., Foltyn-Arfa Kia A., O'Shea D. and Devereux M. 2012. Copper(II) complexes of salicylic acid combining superoxide dismutase mimetic properties with DNA binding and cleaving capabilities exhibit low toxicity and display promising chemotherapeutic potential with fast acting in-vitro cytotoxicity against cisplatin sensitive and resistant cancer cell lines. Journal Of Medicinal Chemistry, 55, 5, pp1957-1968.
• André L.S. Santos, Cátia L. Sodré, Roberta S. Valle, Bianca A. Silva, Érika A. Abi-chacra, Lívia V. Silva, Ana Luiza Souza-Gonçalves, Leandro S. Sangenito, Diego S. Gonçalves, Lucieri O.P. Souza, Vanila F. Palmeira, Claudia M. dAvila-Levy, Lucimar F. Kneipp, Andrew Kellett, Malachy McCann, Marta H. Branquinha. 2012. Antimicrobial Action of Chelating Agents: Repercussions on the Microorganism Development, Virulence and Pathogenesis. Current Medicinal Chemistry, 19, 17, pp2715-2737.
• Andrew Kellett, Malachy McCann, Orla Howe, Mark OConnor and Michael Devereux. 2012. DNA Cleavage Reactions of the Dinuclear Chemotherapeutic Agent Copper(II) Bis-1,10-Phenanthroline Terephthalate. International Journal Of Clinical Pharmacology And Therapeutics, 50, 1, pp79-81.
• Kellett A., OConnor M., McCann M., Howe O., Casey A., McCarron P., McNamara M., Kennedy S., May D. D., Skell P. S., OShea D., Devereux M. 2011. Water-soluble bis(1,10-phenanthroline) octanedioate Cu2+ and Mn2+ complexes with unprecedented nano and picomolar in vitro cytotoxicity: promising leads for chemotherapeutic drug development. Medical Chemistry Communications, 2, 7, pp569-676.
• Kellett A., OConnor M., McCann M., McNamara M., Lynch P., Rosair G., McKee V., Creaven B., Walsh M., McClean S., Foltyn A., OShea D., Howe O., Devereux M. 2011. Bis-phenanthroline copper(II) phthalate complexes are potent in vitro antitumour agents with self-activating metallo-nuclease and DNA binding properties. Dalton Transactions, 40, 5, pp1024-1027.
• Kellett, A., Rosair G., Devereux M., McNamara M., McCann M. 2010. Hexakis(prop-2-enamide)copper(II) bis(perchlorate) and hexakis(prop-2-enamide)manganese(II) bis(perchlorate). Acta Crystallographica Section C, 66,, ppM358-M362.
• Creaven B. S., Czeglédi E., Devereux M., Enyedy É. A., Foltyn-Arfa Kia A., Karcz D., Kellett A., McClean S., Nagy N. V., Noble A., Rockenbauer A.,Szabó-Plánka T., Walsh M. 2010. Biological activity and coordination modes of copper(II) complexes of Schiff base-derived coumarin ligands. Dalton Transactions, 39, 45, pp10854-10865.
• Creaven B. S., Devereux M., Karcz D., Kellett A., McCann M., Noble A., Walsh M. 2009. Copper(II) complexes of coumarin-derived Schiff bases and their anti-Candida activity. Journal Of Inorganic Biochemistry, 103, 9, pp1196-1203.
• Devereux M., O'Shea D., O'Connor M., Grehan H., Connor G., McCann M., Rosair G., Lyng F., Kellett A., Walsh M., Egan D., Thati B. 2007. Synthesis, catalase, superoxide dismutase and antitumour activities of copper(II) carboxylate complexes incorporating benzimidazole, 1,10-phenanthroline and bipyridine ligands: X-ray crystal structures of [Cu(BZA)(2)(bipy)(H2O)], [Cu(SalH)(2)(BZDH)(2)] and [Cu(CH3COO)(2)(5,6-DMBZDH)(2)] (SalH(2) =salicylic acid; BZAH = benzoic acid; BZDH = benzimidazole and 5,6-DMBZDH=5,6-dimethylbenzimidazole). Polyhedron, 26, 15, pp4073-4084.
• Devereux M., O'Shea D., Kellett A., McCann M., Walsh M., Egan D., Deegan C., Kgdziora K., Rosair G., Mulller-Bunz H. 2007. Synthesis, X-ray crystal structures and biomimetic and anticancer activities of novel copper(II)benzoate complexes incorporating 2-(4'-thiazolyl)benzimidazole (thiabendazole), 2-(2-pyridyl)benzimidazole and 1,10-phenanthroline as chelating nitrogen donor ligands. Journal Of Inorganic Biochemistry, 101, 6, pp881-892.
• Devereux M., McCann M., O'Shea D., O'Connor M., Kiely E., McKee V., Naughton D., Fisher A., Kellett A., Walsh M., Egan D., Deegan C. 2006. Synthesis, superoxide dismutase mimetic and anticancer activities of metal complexes of 2,2-dimethylpentanedioic acid(2dmepdaH(2)) and 3,3-dimethylpentanedioic acid(3dmepdaH(2)): X-ray crystal structures of [Cu(3dmepda)(bipy)](2)center dot 6H(2)O and [Cu(2dmepda)(bipy)(EtOH)](2)center dot 4EtOH (bipy=2,2 ' bipyridine). Bioinorganic Chemistry And Applications, 80283,

• Andrew Kellett, Michael Devereux, Malachy McCann, Mark OConnor, Pauraic McCarron, Alan Casey, and Orla Howe, DNA activation by phenanthroline dicarboxylate complexes: new frontiers for metal-based drugs?, Central European Society for Anticancer Drug Research (CESAR) Annual Meeting, 16-JUN-11 - 18-JUN-11, Greifswald University Germany
• Andrew Kellett, DNA activation by phenanthroline dicarboxylate complexes: new frontiers for metal-based drugs?, Chemistry Lecture Seminar Series, 13-APR-11 - , Dublin City University
• Andrew Kellett, Michael Devereux, Mary McNamara, Malachy McCann, Mark OConnor, Orla Howe, Alan Casey, Sean Kennedy, Vickie McKee, Georgina Rosair, Bis-Phenanthroline Copper(II) Complexes of Aromatic and Aliphatic Dicarboxylates are Potent In Vitro Antitumour Agents with `Self-Activating¿ Metallo-Nuclease & DNA Binding Properties, 2nd Symposium on Inorganic Chemistry in Ireland, 17-SEP-10 - , Queens University Belfast
• Pauraic Mc Carron, Malachy McCann, Andrew Kellett, Michael Devereux, Synthesis and Chemotherapeutic Potential of Manganese(II) 1,10-Phenanthroline/Phthalate Complexes, 62nd Irish Universities Chemistry Research Colloquium, 01-JUL-10 - 02-JUL-10, Queens University Belfast
• A. Kellett, M. Devereux, M. McNamara, M. McCann, M. OConnor, D. OShea, G. Rosair, V. McKee, M. Walsh and O. Howe, Anti-Tumor Potential & Mechanistic Studies of New Copper(II) Complexes, Irish Institute of Metal Based Drugs (IIMBD) Symposium, 26-NOV-09 - , Dublin Institute of Technology
• Andrew Kellett, Michael Devereux, Mary McNamara, Malachy McCann, Mark OConnor, Orla Howe, Alan Casey, Sean Kennedy, Vickie McKee, Georgina Rosair, Anti-Tumor Potential & Mechanistic Studies of New Copper(II) Complexes, NUI Maynooth Chemistry Seminar Series, 14-OCT-09 - , National University of Ireland Maynooth
• Michael Devereux, Denis OShea, Mark OConnor, Helen Grehan, Gavin Connor, Malachy McCann, Georgina Rosair, Fiona Lyng, Andrew Kellett, Maureen Walsh, Denise Egan and Bhumika Thati, Copper(II) Superoxide Dismutase Mimetics as Potential Anticancer Drugs, 59th Irish Universities Chemistry Research Colloquium, 13-JUN-07 - 15-JUN-07, Dublin City University
• McCann M., Rowan R., Devereux D., Kellett A., Hilger R., Silver Bullets in Anticancer Chemotherapy, Central European Society for Anticancer Drug Research (CESAR) Annual Meeting, 12-JUL-06 - , University Hospital, Essen, Germany
• Andrew Kelett, Maureen Walsh, Michael Devereux, Helge Muller-Bunz, Vickie McKee and Georgina Rosair, Synthesis, characterisation and biological activity of copper(II) carboxylates incorporating selective N-donor ligands, 3nd Annual Science Research Day ITTD, 31-MAR-05 - , Institute of Technology Tallaght Dublin
• Andrew Kellett, Michael Devereux, Malachy McCann, Denis O'Shea, Maureen Walsh, Bernie Creaven, Helge Muller-Bunz, Copper(II) benzoate complexes incorporating benzimidazole ligands: Synthesis, structures and antifungal activity, 56th Irish Universities Chemistry Research Colloquium, 23-JUN-04 - 25-JUN-04, University of Limerick
• Andrew Kellett, Michael Devereux, Maureen Walsh, Bernie Creaven, Malachy McCann, Denis O'Shea, Helge Muller-Bunz, Novel Cu(II) Benzimidazole Complexes for the treatment of Candida Albicans Related Infections, 8th annual science and computing research colloquium, 26-MAY-04 - 28-MAY-04, Waterford Institute of Technology