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Bioorganometallic chemistry

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, 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      

Dalton Transactions, 2011, 40, 1158-1167.