Selenium Analogues of Anti-Thyroid Drugs

Roy, Gouriprasanna; Mugesh, Govindasamy

doi:10.1080/10426500801898259

Cited by 13 publications

(4 citation statements)

References 42 publications

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“…In recent years, the selenium analogues of MMI, PTU, and MTU attracted considerable attention due to the higher nucleophilic character of the selenium moiety in selones as compared to that of the sulfur in thiones, and the selenium analogues may inhibit the TPO activity by a different mechanism. 11 In general, selones can be synthesized in good yields by using electrophilic selenium, nucleophilic selenium, and carbon diselenide. Guziec et al were the first to report the synthesis of the MMI and its selenium analogue (10) by using an electrophilic selenium route.…”

Section: Selenium Analogues Of Antithyroid Drugsmentioning

confidence: 99%

“…In fact, the thyroid contains more selenium per gram of tissue than any other organ, and therefore, selenium is considered an essential trace element for normal thyroid function and thyroid hormone homeostasis. In recent years, the selenium analogues of MMI, PTU, and MTU attracted considerable attention due to the higher nucleophilic character of the selenium moiety in selones as compared to that of the sulfur in thiones, and the selenium analogues may inhibit the TPO activity by a different mechanism . In general, selones can be synthesized in good yields by using electrophilic selenium, nucleophilic selenium, and carbon diselenide.…”

Section: Selenium Analogues Of Antithyroid Drugsmentioning

confidence: 99%

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Antithyroid Drugs and Their Analogues: Synthesis, Structure, and Mechanism of Action

2013

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Thyroid hormones are essential for the development and differentiation of all cells of the human body. They regulate protein, fat, and carbohydrate metabolism. In this Account, we discuss the synthesis, structure, and mechanism of action of thyroid hormones and their analogues. The prohormone thyroxine (T4) is synthesized on thyroglobulin by thyroid peroxidase (TPO), a heme enzyme that uses iodide and hydrogen peroxide to perform iodination and phenolic coupling reactions. The monodeiodination of T4 to 3,3',5-triiodothyronine (T3) by selenium-containing deiodinases (ID-1, ID-2) is a key step in the activation of thyroid hormones. The type 3 deiodinase (ID-3) catalyzes the deactivation of thyroid hormone in a process that removes iodine selectively from the tyrosyl ring of T4 to produce 3,3',5'-triiodothyronine (rT3). Several physiological and pathological stimuli influence thyroid hormone synthesis. The overproduction of thyroid hormones leads to hyperthyroidism, which is treated by antithyroid drugs that either inhibit the thyroid hormone biosynthesis and/or decrease the conversion of T4 to T3. Antithyroid drugs are thiourea-based compounds, which include propylthiouracil (PTU), methimazole (MMI), and carbimazole (CBZ). The thyroid gland actively concentrates these heterocyclic compounds against a concentration gradient. Recently, the selenium analogues of PTU, MMI, and CBZ attracted significant attention because the selenium moiety in these compounds has a higher nucleophilicity than that of the sulfur moiety. Researchers have developed new methods for the synthesis of the selenium compounds. Several experimental and theoretical investigations revealed that the selone (C═Se) in the selenium analogues is more polarized than the thione (C═S) in the sulfur compounds, and the selones exist predominantly in their zwitterionic forms. Although the thionamide-based antithyroid drugs have been used for almost 70 years, the mechanism of their action is not completely understood. Most investigations have revealed that MMI and PTU irreversibly inhibit TPO. PTU, MTU, and their selenium analogues also inhibit ID-1, most likely by reacting with the selenenyl iodide intermediate. The good ID-1 inhibitory activity of PTU and its analogues can be ascribed to the presence of the -N(H)-C(═O)- functionality that can form hydrogen bonds with nearby amino acid residues in the selenenyl sulfide state. In addition to the TPO and ID-1 inhibition, the selenium analogues are very good antioxidants. In the presence of cellular reducing agents such as GSH, these compounds catalytically reduce hydrogen peroxide. They can also efficiently scavenge peroxynitrite, a potent biological oxidant and nitrating agent.

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Section: Selenium Analogues Of Antithyroid Drugsmentioning

confidence: 99%

Section: Selenium Analogues Of Antithyroid Drugsmentioning

confidence: 99%

Antithyroid Drugs and Their Analogues: Synthesis, Structure, and Mechanism of Action

2013

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“…Among them, the most commonly prescribed ones are methimazole (MMI), 6-methyl-2-thiouracil (MTU), carbimazole (CBZ), and 6- n -propyl-2-thiouracil (PTU). Over decades, a major endeavor has been dedicated to the synthesis, study, and evaluation of functionalized Se containing analogues of several antithyroid drugs. − These compounds have drawn great research interest due to the higher nucleophilicity exerted by the Se moiety in selones compared to the nucleophilic properties of S in thiones. Also, the formation of a −Se–Se– bond with the DIOs enzymes was expected to occur more readily than the −Se–S–. , Besides, it has been proposed that the Se analogues display their inhibitory activities on thyroid peroxidase (TPO) through different mechanisms of action. ,, At the present level of knowledge, it has been suggested that some of them can inhibit TPO through H 2 O 2 scavenging due to their higher susceptibility toward oxidation.…”

Section: Selenized Small Molecule Drugsmentioning

confidence: 99%

Selenization of Small Molecule Drugs: A New Player on the Board

Morán-Serradilla,

Plano,

Sanmartín

et al. 2024

J. Med. Chem.

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There is an urgent need to develop safer and more effective modalities for the treatment of a wide range of pathologies due to the increasing rates of drug resistance, undesired side effects, poor clinical outcomes, etc. Throughout the years, selenium (Se) has attracted a great deal of attention due to its important role in human health. Besides, a growing body of work has unveiled that the inclusion of Se motifs into a great number of molecules is a promising strategy for obtaining novel therapeutic agents. In the current Perspective, we have gathered the most recent literature related to the incorporation of different Se moieties into the scaffolds of a wide range of known drugs and their feasible pharmaceutical applications. In addition, we highlight different representative examples as well as provide our perspective on Se drugs and the possible future directions, promises, opportunities, and challenges of this ground-breaking area of research. ■ SIGNIFICANCE • Significance: The development of novel compounds for the treatment of numerous pathologies has become a priority due to the lack of effective therapeutic options. • Impact: This work highlights the potential of incorporating Se moieties into the scaffold of several drugs to develop novel safer bioactive compounds. • Innovation: This Perspective discusses the development of selenoderivatives of a wide array of drugs and their biological applications and proposes novel avenues to continue exploring this outstanding research area.

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“…Selenium derivative ( B ) has been established as an anticancer agent, particularly for the tongue and prostate adenocarcinoma (Xing et al, 2008 ). In addition, other selenium molecules have been employed as efficient antithyroid drugs in comparison with their sulfur analogs, compounds ( C-F ), Figure 1 (Roy and Mugesh, 2008 ).…”

Section: Introductionmentioning

confidence: 99%

Novel 2-Hydroselenonicotinonitriles and Selenopheno[2, 3-b]pyridines: Efficient Synthesis, Molecular Docking-DFT Modeling, and Antimicrobial Assessment

et al. 2021

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Selenium containing heterocyclic compounds gained great interest as bioactive molecules as of late. This report explores the design, synthesis, characterization, and antimicrobial screening of new pyridine derivatives endowed with selenium moieties. A one-pot multicomponent system with a solvent-free, microwave irradiation environment was employed to afford this series. The spectroscopic techniques were exploited to verify the structures of the synthesized derivatives. Additionally, the agar diffusion method was employed to determine the antimicrobial activity of all the desired compounds. Of all the synthesized molecules, 9b, 12b, 14f, and 16d exhibited well to remarkable antibacterial and antifungal activities. Moreover, derivative 14f demonstrated the most potent antibacterial and antifungal performance. The results were also supported by molecular docking studies, utilizing the MOE (molecular operating environment) which revealed the best binding mode with the highest energy interaction within the binding pocket. Lastly, theoretical DFT calculations were carried out in a gas phase at B3LYP 6-311G (d,p) basis set to predict the molecular geometries and chemical reactivity descriptors. DFT results have been used to illustrate that molecular docking findings and biological activity assessments.

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Selenium Analogues of Anti-Thyroid Drugs

Cited by 13 publications

References 42 publications

Antithyroid Drugs and Their Analogues: Synthesis, Structure, and Mechanism of Action

Antithyroid Drugs and Their Analogues: Synthesis, Structure, and Mechanism of Action

Selenization of Small Molecule Drugs: A New Player on the Board

Novel 2-Hydroselenonicotinonitriles and Selenopheno[2, 3-b]pyridines: Efficient Synthesis, Molecular Docking-DFT Modeling, and Antimicrobial Assessment

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