Abstract
Limitations associated with the production cost, metabolic instability, side-effects, resistance and poor pharmacokinetics of organic protease inhibitors (PIs), which form an essential component of the front line HAART treatment for HIV, have fuelled efforts into finding novel, transition metal-based alternatives. Some of the attractive features of metalbased therapeutics include synthetic simplicity, solubility control, redox capability, expansion of coordination number and topography matching of the complex to the protein’s active site. Building asymmetry into the complex, which may offer better discrimination between host and rogue cell, can readily be achieved through coordination of chiral ligands to the metal centre. Although the scope of this review has been limited to metal-based agents that have been reported to bind/inhibit HIV-1 and parasitic proteases, some desirables, such as high activity, low dosage, minimal toxicity, crossinhibition, unique binding modes and selectivity, have already been delivered. The variability of the d-block metals, coupled with the availability of designer organic ligands, augers well for the future development of clinical metallo-drugs for deployment against protease-associated, fatal diseases.
Keywords: Protease, inhibition, metallo-drug, metal complex, HIV-1, tropical disease, metal-protein interactions.
Current Medicinal Chemistry
Title:Metal-Based Antimicrobial Protease Inhibitors
Volume: 20 Issue: 25
Author(s): A. Kellett, A. Prisecaru, C. Slator, Z. Molphy and M. McCann
Affiliation:
Keywords: Protease, inhibition, metallo-drug, metal complex, HIV-1, tropical disease, metal-protein interactions.
Abstract: Limitations associated with the production cost, metabolic instability, side-effects, resistance and poor pharmacokinetics of organic protease inhibitors (PIs), which form an essential component of the front line HAART treatment for HIV, have fuelled efforts into finding novel, transition metal-based alternatives. Some of the attractive features of metalbased therapeutics include synthetic simplicity, solubility control, redox capability, expansion of coordination number and topography matching of the complex to the protein’s active site. Building asymmetry into the complex, which may offer better discrimination between host and rogue cell, can readily be achieved through coordination of chiral ligands to the metal centre. Although the scope of this review has been limited to metal-based agents that have been reported to bind/inhibit HIV-1 and parasitic proteases, some desirables, such as high activity, low dosage, minimal toxicity, crossinhibition, unique binding modes and selectivity, have already been delivered. The variability of the d-block metals, coupled with the availability of designer organic ligands, augers well for the future development of clinical metallo-drugs for deployment against protease-associated, fatal diseases.
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Cite this article as:
Kellett A., Prisecaru A., Slator C., Molphy Z. and McCann M., Metal-Based Antimicrobial Protease Inhibitors, Current Medicinal Chemistry 2013; 20 (25) . https://dx.doi.org/10.2174/0929867311320250008
DOI https://dx.doi.org/10.2174/0929867311320250008 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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