A Prodrug Approach to Improve the Physico-Chemical Properties and Decrease the Genotoxicity of Nitro Compounds

Chin, Chung Man; Bosquesi, Priscila Longhin; Santos, Jean Leandro dos

doi:10.2174/138161211798194512

Cited by 51 publications

(24 citation statements)

References 46 publications

(92 reference statements)

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“…Moreover, metronidazole therapy can occasionally cause more severe side effects such as pancreatitis, neutropenia, neuropathies, or CNS toxicities 12. These adverse effects could be attenuated with better control over the pharmacokinetics of metronidazole 13. Hence, in this proof‐of‐concept study, we elected to attach metronidazole to ribonucleoside 3′‐phosphates to assess the attributes of this pro‐moiety for orally available drugs (Figure 1).…”

Section: Methodsmentioning

confidence: 99%

Superior Electron‐Transport Ability of π‐Conjugated Redox Molecular Wires Prepared by the Stepwise Coordination Method on a Surface

Nishimori

Kanaizuka

Kurita

et al. 2009

Chemistry An Asian Journal

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Electronic conductivity of molecular wires is a critical fundamental issue in molecular electronics. pi-Conjugated redox molecular wires with the superior long-range electron-transport ability could be constructed on a gold surface through the stepwise ligand-metal coordination method. The beta(d) value, indicating the degree of decrease in the electron-transfer rate constant with distance along the molecular wire between the electrode and the redox active species at the terminal of the wire, were 0.008-0.07 A(-1) and 0.002-0.004 A(-1) for molecular wires of bis(terpyridine)iron and bis(terpyridine)cobalt complex oligomers, respectively. The influences on beta(d) by the chemical structure of molecular wires and the terminal redox units, temperature, electric field, and electrolyte concentration were clarified. The results indicate that facile sequential electron hopping between neighboring metal-complex units within the wire is responsible for the high electron-transport ability.

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Section: Methodsmentioning

confidence: 99%

Superior Electron‐Transport Ability of π‐Conjugated Redox Molecular Wires Prepared by the Stepwise Coordination Method on a Surface

Nishimori

Kanaizuka

Kurita

et al. 2009

Chemistry An Asian Journal

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“…tamoxifen, shown as the nucleotide derivative 14 ). In the case of metronidazole, addition of the phosphate enhances water solubility 50-fold and the prodrug is cleaved rapidly in human serum [25]. Further derivatization of metronidazole through conjugation with a nucleoside 3′-phosphate has been explored as a strategy to enhance oral bioavailability [26].…”

Section: General Considerationsmentioning

confidence: 99%

Prodrugs of Phosphonates and Phosphates: Crossing the Membrane Barrier

Wiemer

2014

Topics in Current Chemistry

148

135

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A substantial portion of metabolism involves transformation of phosphate esters, including pathways leading to nucleotides and oligonucleotides, carbohydrates, isoprenoids and steroids, and phosphorylated proteins. Because the natural substrates bear one or more negative charges, drugs that target these enzymes generally must be charged as well but small charged molecules can have difficulty traversing the cell membrane other than by endocytosis. The resulting dichotomy has stimulated abundant effort to develop effective prodrugs, compounds that carry little or no charge to enable them to transit biological membranes but then able to release the parent drug once inside the target cell. This chapter will present recent studies on advances in prodrug forms, along with representative examples of their application to marketed and developmental drugs.

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“…The goals of prodrug design include but are not limited to the improvement of physicochemical properties [9,10], enhancement of biopharmaceutical profile [10,11], reduction of side effects [9,11], obtaining additive or synergistic effects [6,12], targeted delivery [11,13] or optimization for the route of administration [7,14,15]. …”

Section: Introductionmentioning

confidence: 99%

Prodrugs of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs), More Than Meets the Eye: A Critical Review

Qandil

2012

IJMS

112

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The design and the synthesis of prodrugs for nonsteroidal anti-inflammatory drugs (NSAIDs) have been given much attention by medicinal chemists, especially in the last decade. As a therapeutic group, NSAIDs are among the most widely used prescribed and over the counter (OTC) medications. The rich literature about potential NSAID prodrugs clearly shows a shift from alkyl, aryalkyl or aryl esters with the sole role of masking the carboxylic acid group, to more elaborate conjugates that contain carefully chosen groups to serve specific purposes, such as enhancement of water solubility and dissolution, nitric oxide release, hydrogen sulfide release, antioxidant activity, anticholinergic and acetylcholinesterase inhibitory (AChEI) activity and site-specific targeting and delivery. This review will focus on NSAID prodrugs that have been designed or were, later, found to possess intrinsic pharmacological activity as an intact chemical entity. Such intrinsic activity might augment the anti-inflammatory activity of the NSAID, reduce its side effects or transform the potential therapeutic use from classical anti-inflammatory action to something else. Reports discussed in this review will be those of NO-NSAIDs, anticholinergic and AChEI-NSAIDs, Phospho-NSAIDs and some miscellaneous agents. In most cases, this review will cover literature dealing with these NSAID prodrugs from the year 2006 and later. Older literature will be used when necessary, e.g., to explain the chemical and biological mechanisms of action.

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A Prodrug Approach to Improve the Physico-Chemical Properties and Decrease the Genotoxicity of Nitro Compounds

Cited by 51 publications

References 46 publications

Superior Electron‐Transport Ability of π‐Conjugated Redox Molecular Wires Prepared by the Stepwise Coordination Method on a Surface

Superior Electron‐Transport Ability of π‐Conjugated Redox Molecular Wires Prepared by the Stepwise Coordination Method on a Surface

Prodrugs of Phosphonates and Phosphates: Crossing the Membrane Barrier

Prodrugs of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs), More Than Meets the Eye: A Critical Review

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