The use of transition metal complexes as potential therapeutics and in diagnostic medicine is of considerable importance. The development of organometallic compounds as potential medicinal agents has been on the rise for the past decade, with the development of anticancer and antimicrobial compounds becoming the most prevalent research areas within the field of medicinal chemistry. The introduction of a metal often brings about a metal-specific mechanism of action (to overcome the emergence of resistance to known drugs), is able to generate reactive oxygen species and can alter the permeability of the compound, by altering its lipophilicity.
Our group has focused on two main thrusts. The first focuses on the development of small molecule bioorganometallic compounds based on various pharmacophores (thiosemicarbazones, benzimidazole and aminoquinoline scaffolds), with an emphasis on improving the solubility of potential drug leads and targeting rising resistance. The second approach has been on macromolecular bioorganometallics, based on dendritic scaffolds. In recent years, dendrimers have found potential as molecular tools in biological applications, especially as nanocarriers, diagnostic agents and as chemotherapeutics. The added advantage of dendrimers is their multivalency, which leads to increased interactions between dendrimer-drug conjugates and a target bearing multiple receptors, further improving the selectivity. This work is expected to yield nanomedicinal agents with improved cellular accumulation and activity in chemotherapeutics.
Selected publications
Tameryn Stringer, Maria Alejandra Silva Quintero, Lubbe Wiesner, Gregory S. Smith* and Ebbe Nordlander*
Evaluation of PTA-derived ruthenium(II) and iridium(II) quinoline complexes against chloroquine-sensitive and resistant strains of the Plasmodium falciparum malaria parasite
Journal of Inorganic Biochemistry, 2019, 191, 164-173.
Laa-iqa Rylands, Athi Welsh, Keletso Maepa, Tameryn Stringer, Dale Taylor, Kelly Chibale and Gregory S. Smith*
Structure-activity relation studies of antiplasmodial cyclometallated ruthenium(II), rhodium(III) and iridium(III) complexes of 2-phenylbenzimidazoles
European Journal of Medicinal Chemistry, 2019, 161, 11-21.
Irwin Cassells, Tameryn Stringer, Alan T. Hutton, Sharon Prince and Gregory S. Smith*
Impact of various lipophilic substituents on ruthenium(II), rhodium(III) and iridium(III) salicylaldimineâbased complexes: synthesis, in vitro cytotoxicity studies and DNA interactions
Journal of Biological Inorganic Chemistry, 2018, 23, 763-774
Andrew R. Burgoyne, Catherine H. Kaschula, M. Iqbal Parker and Gregory S. Smith*
Tripodal Half-Sandwich Rhodium and Iridium Complexes Containing Sulfonate and Pyridinyl Entities as Antitumour Agents
European Journal of Inorganic Chemistry, 2017, 5379-5386
Tameryn Stringer, Ronnett Seldon, Nicole Liu, Digby Warner, Christina Tam, Luisa W. Cheng, Kirkwood M. Land, Peter J. Smith, Kelly Chibale and Gregory S. Smith*
Antimicrobial activity of organometallic isonicotinyl and pyrazinyl ferrocenyl-derived complexes
Dalton Transactions, 2017, 46, 9875-9885
Andrew R. Burgoyne, Catherine H. Kaschula, M. Iqbal Parker and Gregory S. Smith*
Synthesis and anticancer evolution of mono- and trinuclear half-sandwich rhodium(III) and iridium(III) complexes based on N,O-salicylaldiminato-sulfonated scaffolds
Journal of Organometallic Chemistry, 2017, 846, 100-104
Muneebah Adams, Carmen De Kock, Peter J. Smith, Kelly Chibale and Gregory S. Smith*
Evaluation of ferrocenyl-containing benzothiazoles as potential antiplasmodial agents
European Journal of Inorganic Chemistry, 2017, 242-246
Muneebah Adams, Tameryn Stringer, Carmen De Kock, Peter J. Smith, Kirkwood M. Land, Nicole Liu, Christina Tam, Luisa W. Cheng, Mathew Njoroge, Kelly Chibale and Gregory S. Smith*
Bioisosteric ferrocenyl-containing quinolines with antiplasmodial and antitrichomonal properties
Dalton Transactions, 2016, 45, 19086-19095
Tameryn Stringer, Carmen de Kock, Hajira Guzgay, John Okombo, Jenny Liu, Sierra Kanetake, Jihwan Kim, Christina Tam, Luisa W. Cheng, Peter J. Smith, Denver T. Hendricks, Kirkwood M. Land, Timothy J. Egan and Gregory S. Smith
Mono- and multimeric ferrocene congeners of quinoline-based polyamines as potential antiparaasitics
Dalton Transactions, 2016, 45, 13415-13426
Nadia Baartzes, Tameryn Stringer, John Okombo, Ronnett Seldon, Digby F. Warner, Carmen de Kock, Peter J. Smith and Gregory S. Smith
Mono- and polynuclear ferrocenylthiosemicarbazones: Synthesis, characterisation and antimicrobial evaluation
Journal of Organometallic Chemistry, 2016, 819, 166-172
Preshendren Govender, Tina Reidel, Paul J. Dyson and Gregory S. Smith
Regulating the anticancer properties of organometallic dendrimers using pyridylferrocene entities: synthesis, cytotoxicity and DNA binding studies
Dalton Transactions, 2016, 45, 9529-9539
Muneebah Adams, Linley Barnard, Carmen de Kock, Peter J. Smith, Lubbe Wiesner, Kelly Chibale and Gregory S. Smith
Cyclopalladated organosilane-tethered thiosemicarbazones: novel strategies for improving antiplasmodial activity
Dalton Transactions, 2016, 45, 5514-5520
Tameryn Stringer, Dale Taylor, Hajira Guzgay, Ajit Shokar, Aaron Au, Peter J. Smith, Denver T. Hendricks, Kirkwood M. Land, Timothy J. Egan and Gregory S. Smith
Polyamine quinolone rhodium complexes: synthesis and pharmacological evaluation as antiparasitic agents against Plasmodium falciparum and Trichomonas vaginalis
Dalton Transactions, 2015, 44, 14906-14917
Andrew R. Burgoyne, Banothile C.E. Makhubela, Mervin Meyer and Gregory S. Smith
Trinuclear Half-Sandwich Ru(II), Rh(III) and Ir(III) Polyester Organometallic Complexes: Synthesis and in vitro Evaluation as Antitumor Agents
European Journal of Inorganic Chemistry, 2015, 1433-1444
Muneebah Adams, Carmen de Kock, Peter J. Smith, Kirkwood M. Land, Nicole Liu, Melissa Hopper, Allyson Hsiao, Andrew R. Burgoyne, Tameryn Stringer, Mervin Meyer, Lubbe Wiesner, Kelly Chibale and Gregory S. Smith
Improved antiparasitic activity by incorporating of organosilane entities into half-sandwich ruthenium(II) and rhodium(III) thiosemicarbqzone complexes
Dalton Transactions, 2015, 44, 2456-2468
Preshendren Govender, Heidi Lemmerhirt, Alan T. Hutton, Bruno Therrien, Patrick J. Bednarski and Gregory S. Smith
First- and Second-Generation Heterometalic Dendrimers Containing Ferrocenyl-Ruthenium(II)-Arene Motifs: Synthesis, Structure, Electrochemistry, and Preliminary Cell Proliferation Studies
Organometallics, 2014, 33, 5535-5545
Yiqun Li, Carmen de Kock, Peter J. Smith, Kelly Chibale* and Gregory S. Smith
Synthesis and Evaluation of a Carbosilane Congener of Ferroquine and Its Corresponding Half-Sandwich Ruthenium and Rhodium Complexes for Antiplasmodial and b-Hematin Inhibition Activity
Organometallics, 2014, 33, 4345-4348
Prinessa Chellan, Kirkwood M. Land, Ajit Shokar, Aaron Au, Seung Hwan An, Dale Taylor, Peter J. Smith, Tina Riedel, Paul J. Dyson, Kelly Chibale and Gregory S. Smith
Synthesis and evaluation of new polynuclear organometallic Ru(II), Rh(III) and Ir(III) pyridyl ester complexes as in vitro Antiparasitic and Antitumor Agents
Dalton Transactions, 2014, 43, 513-526
Prinessa Chellan, Kirkwood M. Land, Ajit Shokar, Aaron Au, Seung Hwan An, Dale Taylor, Peter J. Smith, Kelly Chibale and Gregory S. Smith
Di- and Trinuclear Ruthenium-, Rhodium-, and Iridium-Functionalised Pyridyl Aromatic Ethers: A New Class of Antiparasitic Agents
Organometallics, 2013, 32, 4793-4804
Muneebah Adams, Yiqun Li, Heena Khot, Carmen de Kock, Peter J. Smith, Kirkwood Land, Kelly Chibale and Gregory S. Smith
The synthesis and antiparasitic activity of aryl- and ferrocenyl-derived thiosemicarbazone ruthenium(II)-arene complexes
Dalton Transactions, 2013, 42, 4677-4685
Yiqun Li, Carmen de Kock, Peter J. Smith, Hajira Guzgay, Denver T. Hendricks, Krupa Naran, Valerie Miztahi, Digby F. warner, Kelly Chibale, and Gregory S. Smith
Synthesis, Characterization and Pharmacological Evaluation of Silicon-Containing Aminoquiniline Organometallic Complexes As Antiplasmodial, Antitumor and Antimycobacterial Agents
Organometallics, 2013, 32, 141-150
Preshendren Govender, Lara C. Sudding, Catherine M. Clavel, Paul J. Dyson, Bruno Therrien, and Gregory S. Smith
The influence of RAPTA moieties on the antiproliferative activity of peripheral-functionalised poly(salicylaldiminato)metallodendrimers
Dalton Transactions, 2013, 42, 1267-1277
Prinessa Chellan, Kirkwood M. Land, Ajit Shokar, Aaron Au, Seung Hwan An, Catherine M. Clavel, Paul J. Dyson, Carmen de Kock, Peter J. Smith, Kelly Chibale, and Gregory S. Smith
Exploring the Versatility of Cycloplatinated Thoisemicarbazones as Antitumor and Antiparasitic Agents
Organometallics, 2012, 31, 5791-5799
Preshendren Govender, Bruno Therrien and Gregory S. Smith
Bio-Metallodendrimers – Emerging Strategies in Metal-Based Drug Design
European Journal of Inorganic Chemistry, 2012, 2853-2862
Setshaba D. Khanye, Jiri Gut, Philip J. Rosenthal, Kelly Chibale and Gregory S. Smith
Ferrocenylthiosemicarbazones Conjugated to a Poly(propyleneimine)Dendrimer Scaffold: Synthesis and In Vitro Antimalarial Acitvity
Journal of Organometallic Chemistry, 2011, 696, 3296-3300
Gregory S. Smith and Bruno Therrien
Targeted and multifunctional arene ruthenium chemotherapeutics
Dalton Transactions, 2011, 40, 10793-10800
Preshendren Govender, Anna K. Renfrew, Catherine M. Clavel, Paul J. Dyson, Bruno Therrien, and Gregory S. Smith.
Antiproliferative activity of chelating N,O- and N,N-ruthenium(II) arene functionalised poly(propyleneimine) dendrimers scaffolds