Related Experiment Video
Updated: May 7, 2026
08:23
Chemiluminescence-based Assays for Detection of Nitric Oxide and its Derivatives from Autoxidation and Nitrosated Compounds
Published on: February 16, 2022
Nitroreductase-activated nitric oxide (NO) prodrugs.
Kavita Sharma1, Kundan Sengupta, Harinath Chakrapani
1Department of Chemistry, Indian Institute of Science Education and Research Pune, Pune, Maharashtra, India.
Bioorganic & Medicinal Chemistry Letters
|September 21, 2013
Summary
Researchers developed novel nitric oxide (NO) prodrugs that are activated by a specific enzyme. This targeted approach enhances cancer cell death, showing promise for directed prodrug cancer therapy.
Area of Science:
- Biochemistry
- Pharmacology
- Cancer Research
Background:
- Nitric oxide (NO) plays diverse physiological roles, necessitating targeted delivery to minimize side effects.
- Escherichia coli nitroreductase (NTR) is utilized for directed delivery of therapeutic agents to cancers.
Purpose of the Study:
- To design and evaluate O(2)-(4-Nitrobenzyl) diazeniumdiolates as substrates for NTR-mediated NO release.
- To assess the efficacy of a specific prodrug, compound 4b, in cancer therapy.
Main Methods:
- Synthesis and characterization of O(2)-(4-Nitrobenzyl) diazeniumdiolates.
- Enzymatic metabolism assays using NTR.
- Cell viability assays on cancer cell lines with and without NTR.
Main Results:
- O(2)-(4-Nitrobenzyl) diazeniumdiolates are stable in aqueous buffer.
- NTR efficiently metabolizes these compounds to release NO.
- Compound 4b demonstrated significantly enhanced cytotoxicity against cancer cells in the presence of NTR.
Conclusions:
- O(2)-(4-Nitrobenzyl) diazeniumdiolates are effective NO-releasing prodrugs activated by NTR.
- This enzyme-prodrug system holds potential for targeted nitric oxide-based cancer therapy.
- Further investigation into compound 4b for directed prodrug therapy is warranted.
Related Concept Videos
01:28Nitric Oxide Signaling Pathway
Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure to...
01:23Antihypertensive Drugs: Vasodilators
Vasodilators, primarily affecting the smooth muscles within arterial and venous walls, are commonly used for hypertension treatment. Medications such as minoxidil and hydralazine primarily target arteries and arterioles, while sodium nitroprusside acts on arterioles and venules. Minoxidil, functioning as a prodrug, is metabolized by hepatic sulfotransferase into its active form, minoxidil sulfate, after oral administration. This metabolite binds to the sulfonylurea receptor (SUR) component of...
01:16Antianginal Drugs: Nitrates and β-Blockers
In cardiovascular health, antianginal drugs combat angina pectoris — a condition marked by chest pain owing to diminished blood flow to the heart.
Organic nitrates, such as nitroglycerin, play a pivotal role. Once metabolized, they liberate nitric oxide, a molecular marvel. Nitric oxide triggers guanylyl cyclase and augments cGMP production. This biochemical cascade orchestrates the relaxation of vascular smooth muscles, ushering in vasodilation and enhancing coronary blood flow. Administered...
Organic nitrates, such as nitroglycerin, play a pivotal role. Once metabolized, they liberate nitric oxide, a molecular marvel. Nitric oxide triggers guanylyl cyclase and augments cGMP production. This biochemical cascade orchestrates the relaxation of vascular smooth muscles, ushering in vasodilation and enhancing coronary blood flow. Administered...
01:27Phase I Reactions: Reductive Reactions
Phase I biotransformation reductive reactions are chemical processes that modify drugs by introducing or revealing polar functional groups via reduction. Enzymes called reductases catalyze these reactions, playing a pivotal role in drug metabolism by transforming lipophilic drugs into more polar, water-soluble metabolites for easy excretion. An essential type of reductive reaction is the carbonyl group reduction, where aldehydes and ketones are reduced to alcohols. An example is the...
01:30Prodrugs
Prodrugs are a class of pharmaceutical compounds that undergo a biotransformation process within the body to be converted into a pharmacologically active drug. Prodrugs are designed to improve the therapeutic properties of the parent drug, such as enhancing bioavailability, increasing stability, or reducing toxicity. The concept of prodrugs revolves around modifying the chemical structure of the original drug to make it more effective or convenient for administration.
Prodrugs help overcome...
Prodrugs help overcome...
01:29Preparation of Amines: Reduction of Oximes and Nitro Compounds
Oximes can be reduced to primary amines using catalytic hydrogenation, hydride reduction, or sodium metal reduction. The reduction of aliphatic and aromatic nitro compounds to primary amines takes place by either catalytic hydrogenation or by using active metals like Fe, Zn, and Sn in the presence of an acid.
Though catalytic hydrogenation can reduce nitrobenzenes, the reduction is nonselective in the presence of other functional groups. For instance, if nitrobenzene contains an aldehyde group,...
Though catalytic hydrogenation can reduce nitrobenzenes, the reduction is nonselective in the presence of other functional groups. For instance, if nitrobenzene contains an aldehyde group,...