Synthesis, Hydrolytic Reactivity, and Anticancer Evaluation of N- and O-Triorganosilylated Compounds as New Types of Potential Prodrugs

Chiu, Fang-Ting; Chang, Young Hwan; Ӧzkan, Günay; Zon, Gerald; Fichter, Kenneth C.; Phillips, L.

doi:10.1002/jps.2600710517

Cited by 12 publications

(4 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3,52 To obtain the direct silicon analogue (3), trimethylsilylpyrazole 37 was prepared using a [3 + 2] cycloaddition of trimethylsilylacetylene with ethyl diazoacetate (Scheme 5). A second silicon analogue (41) was designed in which an electron-rich siliconsubstituted aryl ring replaced the silylpyrazole ring. Although sila derivatives 3 and 41 showed almost equivalent inhibition compared to 35 in the p38 MAP kinase enzyme assay, analogue 3 demonstrated slightly enhanced stability to degradation by human liver microsomes.…”

Section: Silicon Isosteres and Transition State Analoguesmentioning

confidence: 99%

“…The ability to control the hydrolysis rate of a silyl ether can be important for medicinal applications related to drug release and delivery in the case of silyl linkers or silicon-based nanoparticles. ,, Utilizing the reactivity of N- and O-silylated compounds, acid-sensitive prodrugs have been previously explored. , For example, silyl ether prodrugs of antiulcer prostaglandins (attached to polybutadiene) have been designed to degrade under the acidic conditions of the stomach . In a recent report, Desimone and co-workers described controlled drug delivery from biocompatible nanoparticles using a bifunctional silyl ether (CO–Si–OC) strategy for a prodrug linkage (Scheme ) .…”

Section: Silyl Ethers and Drug Delivery Strategies Related To Siliconmentioning

confidence: 99%

See 1 more Smart Citation

Organosilicon Molecules with Medicinal Applications

2012

View full text Add to dashboard Cite

The incorporation of silicon and synthesis of organosilicon small molecules provide unique opportunities for medicinal applications. The biological investigation of organosilicon small molecules is particularly interesting because of differences in their chemical properties that can contribute to enhanced potency and improved pharmacological attributes. Applications such as inhibitor design, imaging, drug release technology, and mapping inhibitor binding are discussed.

show abstract

Section: Silicon Isosteres and Transition State Analoguesmentioning

confidence: 99%

Section: Silyl Ethers and Drug Delivery Strategies Related To Siliconmentioning

confidence: 99%

Organosilicon Molecules with Medicinal Applications

2012

View full text Add to dashboard Cite

show abstract

“…Silicon containing ethers are a good option to control drug release from the formulations. It has been reported that O-and N-silicon containing ethers are acid sensitive and explored for their drug release pattern [20] . Controlled hydrolysis rate of silicon containing ethers are important for the drug delivery and release for silicon containing nanoparticles [21] .…”

Section: Silicon Containing Ether In Drug Deliverymentioning

confidence: 99%

Importance of Silicon Atom in the Drug Design Process

Gadhe¹,

Cho²

2012

Journal of the Chosun Natural Science

View full text Add to dashboard Cite

The pharmaceutical industry has an ongoing need for new, safe medicines with genuine biomedical effects. Most of the candidate molecules are far from becomes a drug, because of their pharmacokinetic and pharmacodynamic properties. The introduction of bioisostere to improve properties of molecules and to obtain new class of compound is currently increased. Silicon substitution of carbon of existing drugs is an attractive strategy to search a new candidate with improved biological and physicochemical properties. The fundamental differences between carbon and silicon can lead to improved profile of the silicon containing candidate, and could be exploited to get further benefit in drug design process.

show abstract

“…Silicon and carbon (C) are members of group IV of the Periodic Table of the Elements and share some similarities in their chemistry. The preparation of biologically active organosilicon compounds containing at least one Si-C bond has been an area of investigation for decades [Chiu et al, 1982;Fessenden and Ahlfors, 1967;, 1965, 1966Fessenden and Hartman, 1970;Fessenden and Rittenhouse, 1968;Showell et al, 2006;Tacke, 1977;Tacke and Wannagat, 1977;Tacke and Wannagat, 1979;Tacke and Zilch, 1986]. Silicon and carbon, however, have important chemical differences [Bertrand, 2004]:…”

Section: Bioorganosilicon Chemistrymentioning

confidence: 99%

Novel therapeutics with enhanced biological activity generated by the strategic introduction of silicon isosteres into known drug scaffolds

Gately

West

2007

Drug Development Research

146

View full text Add to dashboard Cite

The strategic replacement of carbon with silicon within biologically prevalidated drug scaffolds can generate focused libraries of pharmaceutically relevant agents with novel, durable and marketable intellectual property. This approach can be cost-effective and of lower developmental risk because known drugs have recognized pharmacology and toxicity profiles, proven safety in humans, and established manufacturing and formulation methods. The change in shape, charge, and lipophilicity that can result from the addition of silicon can favorably alter the biological activity and toxicology of the parent drug. Silicon-containing derivatives of indomethacin are COX-2 selective, suggesting they will not be associated with the classical toxicities associated with nonselective inhibition of the cyclooxygenases. The silicon-indomethacin derivatives also demonstrated superior anti-cancer activity at clinically achievable concentrations when tested in vitro against a human pancreatic cancer cell line, MiaPaCa-2, and a panel of 14 human multiple myeloma cell lines. Bioorganosilicon chemistry represents an attractive approach for emerging biopharmaceutical organizations seeking to rapidly develop a portfolio of novel pharmacological agents that have the potential for enhanced therapeutic and pharmacological benefit. Drug Dev Res 68: [156][157][158][159][160][161][162][163] 2007 r2007 Wiley-Liss, Inc.

show abstract

Synthesis, Hydrolytic Reactivity, and Anticancer Evaluation of N- and O-Triorganosilylated Compounds as New Types of Potential Prodrugs

Cited by 12 publications

References 23 publications

Organosilicon Molecules with Medicinal Applications

Organosilicon Molecules with Medicinal Applications

Importance of Silicon Atom in the Drug Design Process

Novel therapeutics with enhanced biological activity generated by the strategic introduction of silicon isosteres into known drug scaffolds

Contact Info

Product

Resources

About