23060-85-7

Usage

Uses

Used in Pharmaceutical Industry:
4H-Pyran-4-thione,3-hydroxy-2-methyl-(8CI,9CI), or Thiomaltol, is used as a lead compound for the development of slow-binding inhibitors. Its application in this field is primarily due to its potential to inhibit the growth and activity of Bacillus anthracis, the bacterium responsible for anthrax. By targeting and inhibiting the enzyme activity of this bacterium, Thiomaltol can contribute to the development of novel therapeutic strategies against anthrax and other related bacterial infections.

Upstream product

• 118-71-8 Maltol 
• 1223525-45-8 2-methyl-4H-pyran-4-thione-3-β-D-glucopyranoside 
• 546-88-3 acetylhydroxamic acid 

Downstream Products

• 1043932-31-5 C₉H₉ClO₃S 
• 1043933-19-2 C₈H₇ClO₃S 
• 851677-56-0 tris(thiomaltolato)indium(III) 
• 52614-53-6 bis(thiomaltolato)cobalt(II) 
• 1013397-31-3 Ru(2,2'-bipyridine)2(3-hydroxy-2-methyl-4-thiopyrone^(1-))PF₆*CH₂Cl₂ 
• 1220690-23-2 94G₄ 
• 1220690-12-9 94F₅ 
• 1220690-19-6 94F₁₂ 
• 1220690-29-8 3-hydroxy-2-methyl-1-(4-methylphenethyl)pyridine-4(1H)-thione 
• 1220690-10-7 94G₁₀ 
• 1220690-24-3 94G₅ 
• 1220690-40-3 94H₃ 
• 161176-16-5 94H₂ 
• 1220690-14-1 3-hydroxy-1-(4-methoxybenzyl)-2-methylpyridine-4(1H)-thione 

Relevant academic research and scientific papers

Biologically relevant O,S-donor compounds. Synthesis, molybdenum complexation and xanthine oxidase inhibition

Two O,S-donor ligands, hydroxythiopyrone and hydroxythiopyridinone derivatives, were developed and studied, as well as the corresponding O,O-derivatives, with a view to their potential pharmacological applications as xanthine oxidase (XO) inhibitors. The biological assays revealed that the O,S-ligands present high inhibitory activity towards XO (nanomolar order, close to that of the pharmaceutical drug allopurinol), in contrast to the corresponding O,O-analogues. Due to the biomedical relevance of this molybdenum-containing enzyme, the corresponding Mo(vi) complexes were studied both in solution and in the solid state, aimed at identifying the source of the biological properties. The solution studies showed that, in comparison with the O,O-analogues, the Mo(vi) complexes with the O,S-ligands present some stabilization, which is even more pronounced for the reduced Mo(iv) species. The crystal structures of the Mo(vi) complexes with the hydroxythiopyrone revealed good flexibility of the coordination modes, with two structural isomers and two polymorphic forms for a mononuclear and a binuclear species, respectively. These results give some support to mechanistic proposals for the XO inhibition involving the interaction of the thione group with the molybdenum cofactor, thus indicating a role of the sulfur atom in the XO inhibition. The Royal Society of Chemistry.

Synthesis of first row transition metal selenomaltol complexes

We report an efficient, one-step synthesis of the chelator 3-hydroxy-2-methyl-4-selenopyrone (selenomaltol). Complexes of selenomaltol with Fe(iii), Ni(ii), Cu(ii) and Zn(ii) have been prepared and studied by NMR, X-ray crystallography, cyclic voltammetry, EPR and electronic absorption. The Ni(ii) and Cu(ii) complexes show chemically reversible oxidations which are suggested to be ligand-based. Nuclear independent chemical shifts (NICS) analysis is used to compare aromaticity of the heterocyclic rings of selenomaltol and its chelates. The compounds described here should significantly expand the scope and utility of unusual O,Se-donor chelates.

Maltol-derived ruthenium-cymene complexes with tumor inhibiting properties: The impact of ligand-metal bond stability on anticancer activity in vitro

Organometallic rutheniumarene compounds bearing a maltol ligand have been shown to be nearly inactive in in vitro anticancer assays, presumably due to the formation of dimeric Ru" species in aqueous solutions. In an attempt to stabilize such complexes, [Ru(i6-p-cymene)(XY)Cl] (XY = pyrones or thiopyrones) complexes with different substitution pattern of the (thio)pyrone ligands have been synthesized, their structures char-acterized spectroscopically, and their aquation behavior investigated as well as their tumor-inhibiting potency. The aquation behavior of pyrone systems with electron-donating substituents and of thiopyrone complexes was found to be significantly different from that of the maltol-type complex reported previously. However, the formation of the dimer can be excluded as the primary reason for the inactivity of the complex because some of the stable compounds are not active in cancer cell lines either. In contrast, studies of their reactivity towards amino acids demonstrate different reactivities of the pyrone and thiopyrone complexes, and the higher stability of the latter probably renders them active against human tumor cells.

Anti-diabetic effect of organo-chalcogen (sulfur and selenium) zinc complexes with hydroxy-pyrone derivatives on leptin-deficient type 2 diabetes model ob/ob mice

Since the discovery of the anti-diabetic effects of zinc (Zn) complex, we synthesized several Zn complexes and evaluated their effects using the KKAy type 2 diabetes mouse model. Recently, we demonstrated that organo-chalcogen (sulfur and selenium) Zn complexes elicit strong anti-diabetic effects. In this study, we treated leptin-deficient ob/ob mice with organo-chalcogen Zn complexes, and evaluated the resulting anti-diabetic effects in a mouse model of diabetes arising from pathogenic mechanisms different from those in KKAy mice. C57BL/6J ob/ob mice orally received either bis(3-hydroxy-2-methyl-4(H)-pyran-4-thiono)Zn, [Zn(hmpt)2] or bis(3-hydroxy-2-methyl-4(H)-pyran-4-seleno)Zn, [Zn(hmps)2], daily for 28 days. Both Zn complexes elicited potent blood glucose-lowering effects and improved HbA1c values. Moreover, glucose intolerance improved as evidenced by the oral glucose tolerance test, and fasting plasma insulin levels decreased in both types of Zn complex-treated mice. Zn concentrations in the liver and pancreas of [Zn(hmpt)2]-treated mice and in the pancreas of [Zn(hmps)2]-treated mice were increased, respectively. The results suggest that the present Zn complexes mainly exerted an anti-diabetic effect in the liver or pancreas. This study is the first to demonstrate that potent Zn complexes elicit anti-diabetic effects in not only KKAy but also ob/ob mice via a normalizing effect on insulin secretion and fasting blood glucose levels.

Synthesis and: In vivo anticancer evaluation of poly(organo)phosphazene-based metallodrug conjugates

Within this work we aimed to improve the pharmacodynamics and toxicity profile of organoruthenium and -rhodium complexes which had previously been found to be highly potent in vitro but showed unselective activity in vivo. Different organometallic complexes were attached to a degradable poly(organo)phosphazene macromolecule, prepared via controlled polymerization techniques. The conjugation to hydrophilic polymers was designed to increase the aqueous solubility of the typically poorly soluble metal-based half-sandwich compounds with the aim of a controlled, pH-triggered release of the active metallodrug. The synthesized conjugates and their characteristics have been thoroughly studied by means of 31P NMR and UV-Vis spectroscopy, ICP-MS analyses and SEC coupled to ICP-MS. In order to assess their potential as possible anticancer drug candidates, the complexes, as well as their respective macromolecular prodrug formulations were tested against three different cancer cell lines in cell culture. Subsequently, the anticancer activity and organ distribution of the poly(organo)phosphazene drug conjugates were explored in vivo in mice bearing CT-26 colon carcinoma. Our investigations revealed a beneficial influence of this macromolecular prodrug by a significant reduction of adverse effects compared to the free metallodrugs.

Enzymatic activation of a matrix metalloproteinase inhibitor

Matrix metalloproteinase inhibitors (MMPi) possessing a glucose protecting group on the zinc-binding group (ZBG) show a dramatic increase in inhibitory activity upon cleavage by β-glucosidase.

Preparation of 2H-furo[2,3-c]pyran-2-one derivatives and evaluation of their germination-promoting activity

The butenolide, 3-methyl-2H-furo[2,3-c]pyran-2-one (1), has recently been identified as the germination stimulant present in smoke that promotes the germination of seeds from a wide range of plant species. In this paper, we describe the preparation of a number of analogues of 1 and compare their efficacy in promoting seed germination of three highly smoke-responsive plant species, Lactuca sativa L. cv. Grand Rapids (Asteraceae), Emmenanthe penduliflora Benth. (Hydrophyllaceae), and Solanum orbiculatum Poir. (Solanaceae). The results show that the methyl substituent at C-3 in 1 is important for germination-promoting activity while substitution at C-7 reduces activity. In contrast, bioactivity is mostly retained with analogues substituted at C-4 or C-5.

ZINC-BINDING GROUPS FOR METALLOPROTEIN INHIBITORS

The present invention relates to metalloprotein inhibitors comprising: a. an organic backbone molecule (Pep) and at least one zinc binding group (ZBG) covalently attached thereto; or b. at least one ZBG substituted by a side chain that comprises one or more amido and/or amino moieties, wherein the ZBG is of formula (I): wherein the wavy line represents a Pep molecule or a side chain that is an R3 or an R4 group which comprises one or more amido and/or amino moieties, and wherein X is O or S and each R1, R2, R3, and R4 is individually hydrogen or an organic radical. The metalloprotein inhibitors are useful for preventing or treating a pathological disease, condition, or symptom that is associated with pathological metalloprotein activity and/or that is alleviated by inhibition of said activity.