Preparation, characterization and in vivo conversion of new water-soluble sulfenamide prodrugs of carbamazepine

Hemenway, Jeffrey N.; Nti-Addae, Kwame; Guarino, Victor R.; Stella, Valentino J.

doi:10.1016/j.bmcl.2007.09.045

Cited by 24 publications

(11 citation statements)

References 16 publications

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“…The rapid N-S(II) reactivity toward cellular thiols is the basis of the mechanism of action of many antibiotics (Turos et al, 2002;Turos, 2005;Revell et al, 2007;Prosen et al, 2011;Ramaraju et al, 2012;Shang et al, 2013), pesticides (Chiu et al, 1975;Umetsu et al, 1980;Fukuto et al, 1983;Wallace and Zerba, 1989), and prodrug candidates (Olbe et al, 2003;Hemenway, 2006;Hemenway et al, 2007;Nti-Addae, 2008;Proença et al, 2011;Huttunen et al, 2012). Similarly, the reactivity of N-S(II) compounds to other common functional groups found in the cell (other than thiols) is not detected, showing that the main reactivity of N-S(II) compounds in the cellular environment comes from -SH groups and not from others (alcohols, amines, carboxylic acids, etc.)…”

Section: Literature Review On N-s-thiol Reactivitymentioning

confidence: 99%

An Apparent Binary Choice in Biochemistry: Mutual Reactivity Implies Life Chooses Thiols or Nitrogen-Sulfur Bonds, but Not Both

2019

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A fundamental goal of biology is to understand the rules behind life's use of chemical space. Established work focuses on why life uses the chemistry that it does. Given the enormous scope of possible chemical space, we postulate that it is equally important to ask why life largely avoids certain areas of chemical space. The nitrogen-sulfur bond is a prime example, as it rarely appears in natural molecules, despite the very rich N-S bond chemistry applied in various branches of industry (e.g., industrial materials, agrochemicals, pharmaceuticals). We find that, out of more than 200,000 known, unique compounds made by life, only about 100 contain N-S bonds. Furthermore, the limited number of N-S bond-containing molecules that life produces appears to fall into a few very distinctive structural groups. One may think that industrial processes are unrelated to biochemistry because of a greater possibility of solvents, catalysts, and temperatures available to industry than to the cellular environment. However, the fact that life does rarely make N-S bonds, from the plentiful precursors available, and has evolved the ability to do so independently several times, suggests that the restriction on life's use of N-S chemistry is not in its synthesis. We present a hypothesis to explain life's extremely limited usage of the N-S bond: that the N-S bond chemistry is incompatible with essential segments of biochemistry, specifically with thiols. We support our hypothesis by (1) a quantitative analysis of the occurrence of N-S bond-containing natural products and (2) reactivity experiments between selected N-S compounds and key biological molecules. This work provides an example of a reason why life nearly excludes a distinct region of chemical space. Combined with future examples, this potentially new field of research may provide fresh insight into life's evolution through chemical space and its origin and early evolution.

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Section: Literature Review On N-s-thiol Reactivitymentioning

confidence: 99%

An Apparent Binary Choice in Biochemistry: Mutual Reactivity Implies Life Chooses Thiols or Nitrogen-Sulfur Bonds, but Not Both

2019

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“…The aqueous solubility of the N -cysteamine derivative exceeded 100 mg/mL, at pH 2.6, and its predicted shelf-life (t 90% ) was 320 days, at pH 4.0 and 25 °C. After an IV dose of 133 in rats, the parent drug was immediately seen in plasma, whereas no intact drug was observed, suggesting that the conversion of prodrug to parent drug occurred rapidly and most probably via reaction with glutathione ( Figure 53 ) [ 177 ].…”

Section: Drugs and Diseasesmentioning

confidence: 99%

Amino Acids in the Development of Prodrugs

Vale

Ferreira

Matos³

et al. 2018

Molecules

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Although drugs currently used for the various types of diseases (e.g., antiparasitic, antiviral, antibacterial, etc.) are effective, they present several undesirable pharmacological and pharmaceutical properties. Most of the drugs have low bioavailability, lack of sensitivity, and do not target only the damaged cells, thus also affecting normal cells. Moreover, there is the risk of developing resistance against drugs upon chronic treatment. Consequently, their potential clinical applications might be limited and therefore, it is mandatory to find strategies that improve those properties of therapeutic agents. The development of prodrugs using amino acids as moieties has resulted in improvements in several properties, namely increased bioavailability, decreased toxicity of the parent drug, accurate delivery to target tissues or organs, and prevention of fast metabolism. Herein, we provide an overview of models currently in use of prodrug design with amino acids. Furthermore, we review the challenges related to the permeability of poorly absorbed drugs and transport and deliver on target organs.

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“…An in vivo pharmacokinetic assay with i.v. administration demonstrated that compound 81 was rapidly converted to CBZ [111].…”

Section: Other Chemical Prodrugsmentioning

confidence: 99%

The Prodrug Approach: A Successful Tool for Improving Drug Solubility

et al. 2015

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Prodrug design is a widely known molecular modification strategy that aims to optimize the physicochemical and pharmacological properties of drugs to improve their solubility and pharmacokinetic features and decrease their toxicity. A lack of solubility is one of the main obstacles to drug development. This review aims to describe recent advances in the improvement of solubility via the prodrug approach. The main chemical carriers and examples of successful strategies will be discussed, highlighting the advances of this field in the last ten years.

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Preparation, characterization and in vivo conversion of new water-soluble sulfenamide prodrugs of carbamazepine

Cited by 24 publications

References 16 publications

An Apparent Binary Choice in Biochemistry: Mutual Reactivity Implies Life Chooses Thiols or Nitrogen-Sulfur Bonds, but Not Both

An Apparent Binary Choice in Biochemistry: Mutual Reactivity Implies Life Chooses Thiols or Nitrogen-Sulfur Bonds, but Not Both

Amino Acids in the Development of Prodrugs

The Prodrug Approach: A Successful Tool for Improving Drug Solubility

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