Benzothiazolyl substituted iminothiazolidinones and benzamido-oxothiazolidines as potent and partly selective aldose reductase inhibitors

Saeed, Aamer; Tehseen, Yildiz; Rafique, Hummera; Furtmann, Norbert; Bajorath, Jürgen; Flörke, Ülrich; Iqbal, Jamshed

doi:10.1039/c4md00206g

Cited by 20 publications

(14 citation statements)

References 29 publications

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“…The rationale for the synthesis of these compounds is related to the well-known pharmacological activity of two important pharmacophores, namely, 5-amino-1,3,4-thiadiazole and 4,5-dihydrothiazoline. Both of these heterocyclic pharmacophores are components of many pharmacologically active compounds [ 51 , 52 , 53 ]. The thiadiazole and dihydrothiazoline moieties are linked via a thio-bridge to the anhydro skeleton of levoglucosenone.…”

Section: Methodsmentioning

confidence: 99%

Evaluation of the Mycobactericidal Effect of Thio-functionalized Carbohydrate Derivatives

et al. 2017

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Sugars with heteroatoms other than oxygen have attained considerable importance in glycobiology and in drug design since they are often more stable in blood plasma due to their resistance to enzymes, such as glycosidases, phosphorylases and glycosyltransferases. The replacement of oxygen atoms in sugars with sulfur forms thio-sugars, which are potentially useful for the treatment of diabetes and some bacterial and viral infections. Here, we evaluated the antibacterial activity of thio-functionalized carbohydrate derivatives. A set of 21 compounds was screened against acid-fast Mycobacterium tuberculosis (Mtb), gram-negative Escherichia coli and gram-positive Staphylococcus aureus. The tested carbohydrate derivatives were most effective against tubercle bacilli, with as many as five compounds (thioglycoside 6, thiosemicarbazone 16A, thiosemicarbazone 20, aminothiadiazole 23, and thiazoline 26) inhibiting its growth with MIC50 ≤ 50 µM/CFU. Only two compounds (aminothiadiazole 23 and thiazoline 26) were able to inhibit the growth of E. coli at concentrations below 1 mM, and one of them, aminothiadiazole 23, inhibited the growth of S. aureus at a concentration ≤1 mM. The five compounds affecting the growth of mycobacteria were either thiodisaccharides (6, 16A, and 20) or thioglycosides (23 and 26). All of these compounds (6, 16A, 20, 23, and 26) were able to inhibit the growth of Mtb deposited within human macrophages. However, three of the five selected compounds (6, 23, and 26) exhibited relatively high cytotoxicity in mouse fibroblasts at micromolar concentrations. The selected thio-sugars are very promising compounds, thus making them candidates for further modifications that would decrease their cytotoxicity against eukaryotic cells without affecting their antimycobacterial potential.

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Section: Methodsmentioning

confidence: 99%

Evaluation of the Mycobactericidal Effect of Thio-functionalized Carbohydrate Derivatives

et al. 2017

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“…Previous reports to the synthesis of ( 3 ) involve the reaction of 2-aminophenol with potassium hydroxide in liquid carbon disulfide along with long reaction times, and difficult workup [ 15 ]. Earlier we had also reported a similar cyclo-condensation reaction promoted by microwave radiation [ 10 ], however currently it was found that simple fusion of the two reactants under conventional heating gave the product in better yield. Consequently, by modification of our method [ 10 ], solventless synthesis of benzo[ d ]oxazole-2-thiol ( 3 ) was achieved by direct cyclocondensation of 2-aminothio phenol ( 1 ) with thiourea ( 2 ) in absence of solvent or catalyst in good yield and high purity.…”

Section: Resultsmentioning

confidence: 94%

“…Recent efforts in the preparation of substituted-thio-benzo[ d ]oxazoles have been reported [ 8 , 9 ]. In particular, the title compound was prepared as a key intermediate towards a variety of S -substituted heterocycles in order to explore them for comparison of their biological activities with corresponding well-known N -substituted analogues [ 10 ]. Thus, the acid hydrazide synthesized by the condensation of methyl 2-(benzo[ d ]oxazol-2-ylthio) acetate with hydrazine hydrate could be converted into thiosemicarbazides by the reaction with substituted isothiocyanates [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis, conformation and Hirshfeld surface analysis of benzoxazole methyl ester as a versatile building block for heterocycles

Saeed

Shabir

Hökelek

et al. 2021

Heliyon

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Solventless cyclocondensation of 2-aminothiophenol with thiourea afforded the benzo[ d ]oxazole-2-thiol ( 3a ) capable of existing also in the tautomeric form benzo[ d ]oxazole-2(3 H )-thione ( 3b ). Acylation with methyl chloroacetate in dry ethanol in absence of any base or catalyst selectively afforded the S -substituted ester 2-(methoxycarbonylmethylthio)benzo[ d ]oxazole ( 4a ) in preference to the corresponding N -substituted ester N -(methoxycarbonylmethyl)thioxobenzoxazole ( 4b ). Quantum chemical calculations were conducted to determine the conformational landscape and NBO population analysis showed the strong electronic delocalization via resonance interactions on the 2-mercaptobenzaxazole group. The anomeric effect and the occurrence of a 1,4-S···O intramolecular interactions suggest the relevance of chalcogen bonding in the conformational preference. The Hirshfeld surface analysis of the crystal structure indicates that the most important contributions for the crystal packing are from H⋯H (33.2%), H⋯O/O⋯H (19.9%) and H⋯C/C⋯H (17.8%) interactions. Hydrogen bonding and van der Waals interactions are the dominant interactions in the crystal packing. Computational chemistry indicates that in the crystal, the C–H⋯O hydrogen-bond energy is 44.8 kJ mol −1 .

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“…Similarly, the inhibitions of amidohydrolase enzyme is taken for a good chance to treat infection cause by Helicobacter pylori parasite (Saeed et al, 2014). Decades ago, about thousands of urease enzyme inhibitors were identified such as benzo [d]thaizole hydrazone, phosphoramidate, urea analogues, hydroxamic acids, chromanones, polyphenols and alkaniod (Vassiliou et al, 2010).…”

Section: A R T I C L E I N F O Abstractmentioning

confidence: 99%

Quantitative Structure-Activity Relationship and Molecular Docking Studies of Hydroxamic Acid Derivatives as Novel Class Inhibitors Against Helicobacter Pylori Urease

Ibrahim

Uzairu

Sagagi

2019

jCEC

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In order to develop quantitative structure-activity relationship (QSAR), for predicting antiulcer activity of hydroxamic acid analogues use as dataset and their antiulcer activity were obtained from the literature. Density Functional Theory (DFT) using B3LYP/6-31G* quantum chemical calculation method was used to find the optimized geometry of the studied compounds. Eight types of molecular descriptors were used to find out the relation between antipeptic ulcer (APU) activity and structural properties. Relevant molecular descriptors were selected by Genetic Function Algorithms (GFA). The best model obtained was given a distinct validated, good and robust statistical parameters which include; square correlation coefficient R2 value of (0.9989), adjusted determination coefficient, R2adj value of (0.9984), Leave one out cross validation determination coefficient Q2 value of (0.9948) and external validation as predicted determination coefficient R2 value of(0.8409). Molecular docking analysis find out that, the best lead-compound with the higher negative value score of (-8.5 kcal/mol) were formed hydrophobic interaction and H-bonding with amino acid residue between the inhibitors compounds with their respective receptor.

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Benzothiazolyl substituted iminothiazolidinones and benzamido-oxothiazolidines as potent and partly selective aldose reductase inhibitors

Abstract: Two new series of oxothiazolidine benzoate and acetate derivatives were synthesized and evaluated as aldehyde reductase (ALR1) and aldose reductase (ALR2) inhibitors.

Cited by 20 publications

References 29 publications

Evaluation of the Mycobactericidal Effect of Thio-functionalized Carbohydrate Derivatives

Evaluation of the Mycobactericidal Effect of Thio-functionalized Carbohydrate Derivatives

Synthesis, conformation and Hirshfeld surface analysis of benzoxazole methyl ester as a versatile building block for heterocycles

Quantitative Structure-Activity Relationship and Molecular Docking Studies of Hydroxamic Acid Derivatives as Novel Class Inhibitors Against Helicobacter Pylori Urease

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